View source for Vaccine

{{Short description|Pathogen-derived preparation that provides acquired immunity to an infectious disease}}
{{Other uses}}
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{{Infobox medical intervention (new)
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| caption      = [[Smallpox vaccine]] and equipment for administering it
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| MeshID       = D014612
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{{Vaccination}}

A '''vaccine''' is a biological [[Dosage form|preparation]] that provides active [[acquired immunity]] to a particular [[infectious disease|infectious]] or [[cancer|malignant]] disease.<ref name="iac39">{{cite journal |title=Expanded Practice Standards |journal=Iowa Administrative Code |date=2019 |url=https://www.legis.iowa.gov/docs/iac/rule/02-27-2019.657.39.11.pdf |access-date=16 January 2023 |archive-date=19 January 2023 |archive-url=https://web.archive.org/web/20230119023633/https://www.legis.iowa.gov/docs/iac/rule/02-27-2019.657.39.11.pdf |url-status=live }}</ref><ref>{{Cite web|title=Immunization: The Basics|url=https://www.cdc.gov/vaccines/vac-gen/imz-basics.htm|website=Centers for Disease Control and Prevention|date=22 November 2022|access-date=8 July 2023|archive-date=12 July 2023|archive-url=https://web.archive.org/web/20230712151624/https://www.cdc.gov/vaccines/vac-gen/imz-basics.htm|url-status=live}}</ref> The safety and effectiveness of vaccines has been widely studied and verified.<ref name="AmannaSlifka2018">{{cite book | title =Vaccination Strategies Against Highly Variable Pathogens | last1 = Amanna | first1 = Ian J. | last2 = Slifka | first2 = Mark K. | chapter = Successful Vaccines |editor1= Lars Hangartner|editor2= Dennis R. Burton | series=Current Topics in Microbiology and Immunology, vol. 428 | date = 2018 | volume = 428 | pages = 1–30 | publisher = Springer | doi = 10.1007/82_2018_102 | pmid = 30046984 | pmc = 6777997 | isbn = 978-3-030-58003-2 | quote = "The effect of vaccines on public health is truly remarkable. One study examining the impact of childhood vaccination on the 2001 US birth cohort found that vaccines prevented 33,000 deaths and 14 million cases of disease (Zhou et al. 2005). Among 73 nations supported by the GAVI alliance, mathematical models project that vaccines will prevent 23.3 million deaths from 2011–2020 compared to what would have occurred if there were no vaccines available (Lee et al. 2013). Vaccines have been developed against a wide assortment of human pathogens."}}</ref><ref name="NYT-20201120">{{cite news |last=Zimmer |first=Carl |author-link=Carl Zimmer |date=20 November 2020 |title=2 Companies Say Their Vaccines Are 95% Effective. What Does That Mean? You might assume that 95 out of every 100 people vaccinated will be protected from Covid-19. But that's not how the math works. |work=[[The New York Times]] |url=https://www.nytimes.com/2020/11/20/health/covid-vaccine-95-effective.html |access-date=21 November 2020 |archive-date=22 November 2020 |archive-url=https://web.archive.org/web/20201122231014/https://www.nytimes.com/2020/11/20/health/covid-vaccine-95-effective.html |url-status=live }}</ref> A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the [[immune system]] to recognize the agent as a threat, destroy it, and recognize further and destroy any of the microorganisms associated with that agent that it may encounter in the future.

Vaccines can be [[prophylaxis|prophylactic]] (to prevent or alleviate the effects of a future [[infection]] by a natural or "wild" [[pathogen]]), or [[therapeutic vaccines|therapeutic]] (to fight a disease that has already occurred, such as [[cancer vaccine|cancer]]).<ref name="pmid26214521">{{cite journal | vauthors = Melief CJ, van Hall T, Arens R, Ossendorp F, van der Burg SH | title = Therapeutic cancer vaccines | journal = The Journal of Clinical Investigation | volume = 125 | issue = 9 | pages = 3401–3412 | date = September 2015 | pmid = 26214521 | pmc = 4588240 | doi = 10.1172/JCI80009 }}</ref><ref name="pmid26861670">{{cite journal | vauthors = Bol KF, Aarntzen EH, Pots JM, Olde Nordkamp MA, van de Rakt MW, Scharenborg NM, de Boer AJ, van Oorschot TG, Croockewit SA, Blokx WA, Oyen WJ, Boerman OC, Mus RD, van Rossum MM, van der Graaf CA, Punt CJ, Adema GJ, Figdor CG, de Vries IJ, Schreibelt G | title = Prophylactic vaccines are potent activators of monocyte-derived dendritic cells and drive effective anti-tumor responses in melanoma patients at the cost of toxicity | journal = Cancer Immunology, Immunotherapy | volume = 65 | issue = 3 | pages = 327–339 | date = March 2016 | pmid = 26861670 | pmc = 4779136 | doi = 10.1007/s00262-016-1796-7 }}</ref><ref>{{cite journal |vauthors=Brotherton J |title=HPV prophylactic vaccines: lessons learned from 10 years experience |journal= Future Virology|volume=10 |issue=8 |pages=999–1009 |year=2015 |doi=10.2217/fvl.15.60 }}</ref><ref name="pmid24748633">{{cite journal | vauthors = Frazer IH | title = Development and implementation of papillomavirus prophylactic vaccines | journal = Journal of Immunology | volume = 192 | issue = 9 | pages = 4007–4011 | date = May 2014 | pmid = 24748633 | doi = 10.4049/jimmunol.1490012 | doi-access = free }}</ref> Some vaccines offer full [[sterilizing immunity]], in which infection is prevented.<ref>{{Cite journal|last=Ledford|first=Heidi|date=17 August 2020|title=What the immune response to the coronavirus says about the prospects for a vaccine|journal=Nature|volume=585|issue=7823|pages=20–21|doi=10.1038/d41586-020-02400-7|pmid=32811981|bibcode=2020Natur.585...20L|s2cid=221180503|doi-access=free}}</ref>

The administration of vaccines is called [[vaccination]]. Vaccination is the most effective method of preventing infectious diseases;<ref>*United States Centers for Disease Control and Prevention (2011). [https://www.cdc.gov/oid/docs/ID-Framework.pdf ''A CDC framework for preventing infectious diseases.''] {{webarchive|url=https://web.archive.org/web/20170829133723/https://www.cdc.gov/oid/docs/ID-Framework.pdf |date=29 August 2017 }} Accessed 11 September 2012. "Vaccines are our most effective and cost-saving tools for disease prevention, preventing untold suffering and saving tens of thousands of lives and billions of dollars in healthcare costs each year."
*American Medical Association (2000). [http://www.immunizationinfo.org/es/pressroom/2000-06-01/vaccines-and-infectious-diseases-putting-risk-perspective ''Vaccines and infectious diseases: putting risk into perspective.''] {{webarchive|url=https://web.archive.org/web/20150205193837/http://www.immunizationinfo.org/es/pressroom/2000-06-01/vaccines-and-infectious-diseases-putting-risk-perspective |date=5 February 2015 }} Accessed 11 September 2012. "Vaccines are the most effective public health tool ever created."
*Public Health Agency of Canada. [http://www.phac-aspc.gc.ca/im/vpd-mev/index-eng.php ''Vaccine-preventable diseases.''] {{webarchive|url=https://web.archive.org/web/20150313131826/http://www.phac-aspc.gc.ca/im/vpd-mev/index-eng.php |date=13 March 2015 }} Accessed 11 September 2012. "Vaccines still provide the most effective, longest-lasting method of preventing infectious diseases in all age groups."
*United States National Institute of Allergy and Infectious Diseases (NIAID). [http://virtualbiosecuritycenter.org/wp-content/uploads/2012/01/Library-NIAID-Biodefense-Research-Agenda-for-Category-B-and-C-Priority-Pathogens.pdf ''NIAID Biodefense Research Agenda for Category B and C Priority Pathogens.''] {{webarchive|url=https://web.archive.org/web/20160304065419/http://virtualbiosecuritycenter.org/wp-content/uploads/2012/01/Library-NIAID-Biodefense-Research-Agenda-for-Category-B-and-C-Priority-Pathogens.pdf |date=4 March 2016 }} Accessed 11 September 2012. "Vaccines are the most effective method of protecting the public against infectious diseases."</ref> widespread immunity due to vaccination is largely responsible for the [[Eradication of infectious diseases|worldwide eradication]] of [[smallpox]] and the restriction of diseases such as [[polio]], [[measles]], and [[tetanus]] from much of the world. The [[World Health Organization]] (WHO) reports that licensed vaccines are available for twenty-five different [[vaccine-preventable diseases|preventable infections]].<ref>{{cite web | title=Global Vaccine Action Plan | website=[[World Health Organization]] (WHO) | date=14 June 2020 | url=https://www.who.int/teams/immunization-vaccines-and-biologicals/strategies/global-vaccine-action-plan | access-date=7 March 2025 | archive-url=https://web.archive.org/web/20140414035449/http://www.who.int/immunization/global_vaccine_action_plan/GVAP_doc_2011_2020/en/ | archive-date=14 April 2014}}</ref>

The first recorded use of [[inoculation]] to prevent smallpox (see [[variolation]]) occurred in the 16th century in China, with the earliest hints of the practice in China coming during the 10th century.{{sfn|Williams|2010|p=60}} It was also the first disease for which a vaccine was produced.<ref name="pmid17633292">{{cite journal | vauthors = Lombard M, Pastoret PP, Moulin AM | s2cid = 6688481 | title = A brief history of vaccines and vaccination | journal = Revue Scientifique et Technique | volume = 26 | issue = 1 | pages = 29–48 | date = April 2007 | pmid = 17633292 | doi = 10.20506/rst.26.1.1724 | doi-access = free }}</ref><ref name="pmid6319980">{{cite journal | vauthors = Behbehani AM | title = The smallpox story: life and death of an old disease | journal = Microbiological Reviews | volume = 47 | issue = 4 | pages = 455–509 | date = December 1983 | pmid = 6319980 | pmc = 281588 | doi = 10.1128/MMBR.47.4.455-509.1983}}</ref> The folk practice of [[inoculation]] against [[smallpox]] was brought from Turkey to Britain in 1721 by [[Lady Mary Wortley Montagu]].<ref name="Montagu's bold experiment">{{cite web | last=Ferguson | first=Donna | title=How Mary Wortley Montagu's bold experiment led to smallpox vaccine – 75 years before Jenner | website=[[The Guardian]] | date=28 March 2021 | url=http://www.theguardian.com/society/2021/mar/28/how-mary-wortley-montagus-bold-experiment-led-to-smallpox-vaccine-75-years-before-jenner | access-date=11 July 2022 | archive-date=11 July 2022 | archive-url=https://web.archive.org/web/20220711092547/https://www.theguardian.com/society/2021/mar/28/how-mary-wortley-montagus-bold-experiment-led-to-smallpox-vaccine-75-years-before-jenner | url-status=live }}</ref>
The terms ''vaccine'' and ''vaccination'' are derived from ''Variolae vaccinae'' (smallpox of the cow), the term devised by [[Edward Jenner]] (who both developed the concept of vaccines and created the first vaccine) to denote [[cowpox]]. He used the phrase in 1798 for the long title of his ''Inquiry into the Variolae vaccinae Known as the Cow Pox'', in which he described the protective effect of cowpox against smallpox.<ref name=Baxby1999>{{cite journal | vauthors = Baxby D | author-link = Derrick Baxby|title = Edward Jenner's Inquiry; a bicentenary analysis | journal = Vaccine | volume = 17 | issue = 4 | pages = 301–307 | date = January 1999 | pmid = 9987167 | doi = 10.1016/s0264-410x(98)00207-2 }}</ref> In 1881, to honor Jenner, [[Louis Pasteur]] proposed that the terms should be extended to cover the new protective inoculations then being developed.<ref name=Pasteur1881>{{cite journal|last=Pasteur|first=Louis | name-list-style = vanc |title=Address on the Germ Theory|journal=Lancet|year=1881|volume=118|issue=3024|pages=271–272|doi=10.1016/s0140-6736(02)35739-8}}</ref> The science of vaccine development and production is termed ''[[wikt:vaccinology|vaccinology]]''.
[[File:Vaccination-introduction-and-cases-or-deaths-scaled.jpg|thumb|400px|Infectious diseases before and after a vaccine was introduced. Vaccinations have a direct effect on the diminishment of the number of cases and contributes indirectly to a diminishment of the number of deaths.]]

==Effectiveness==
<!--This section is linked from [[Mumps]].-->
[[File:RougeoleDP.jpg|thumb|A child with [[measles]], a vaccine-preventable disease<ref>{{cite web| url=https://www.cdc.gov/measles/vaccination.html| title=Measles Vaccination CDC| date=5 February 2018| access-date=13 November 2018| archive-date=19 November 2019| archive-url=https://web.archive.org/web/20191119142614/https://www.cdc.gov/measles/vaccination.html| url-status=live}}</ref>]]

There is overwhelming scientific consensus that vaccines are a very safe and effective way to fight and eradicate infectious diseases.<ref>{{cite journal | vauthors = Orenstein WA, Bernier RH, Dondero TJ, Hinman AR, Marks JS, Bart KJ, Sirotkin B | title = Field evaluation of vaccine efficacy | journal = Bulletin of the World Health Organization | volume = 63 | issue = 6 | pages = 1055–1068 | date = 1985 | pmid = 3879673 | pmc = 2536484 }}</ref><ref>{{cite web|url=https://hub.jhu.edu/2017/01/11/vaccines-autism-public-health-expert/|title=The science is clear: Vaccines are safe, effective, and do not cause autism|date=11 January 2017|website=The Hub|access-date=16 April 2019|archive-date=28 September 2017|archive-url=https://web.archive.org/web/20170928005601/https://hub.jhu.edu/2017/01/11/vaccines-autism-public-health-expert/|url-status=live}}</ref><ref>{{cite journal | vauthors = Ellenberg SS, Chen RT | title = The complicated task of monitoring vaccine safety | journal = Public Health Reports | volume = 112 | issue = 1 | pages = 10–20; discussion 21 | date = 1997 | pmid = 9018282 | pmc = 1381831 }}</ref><ref>{{cite web|url=http://www.healthychildren.org/English/safety-prevention/immunizations/Pages/Vaccine-Safety-The-Facts.aspx|title=Vaccine Safety: The Facts|website=HealthyChildren.org|date=10 October 2018 |access-date=16 April 2019|archive-date=16 April 2019|archive-url=https://web.archive.org/web/20190416034623/https://www.healthychildren.org/English/safety-prevention/immunizations/Pages/Vaccine-Safety-The-Facts.aspx|url-status=live}}</ref> The [[immune system]] recognizes vaccine agents as foreign, destroys them, and "remembers" them. When the [[virulence|virulent]] version of an agent is encountered, the body recognizes the protein coat on the agent, and thus is prepared to respond, by first neutralizing the target agent before it can enter cells, and secondly by recognizing and destroying infected cells before that agent can multiply to vast numbers.<ref name="Mak">{{cite book |last1=Mak |first1=Tak W. |last2=Saunders |first2=Mary E. |last3=Jett |first3=Bradley D. |title=Primer to The immune response |date=2014 |publisher=Academic Cell |location=Burlington, MA |isbn=978-0-12-385245-8 |pages=3–20 |edition=2nd |chapter-url=https://www.sciencedirect.com/science/article/pii/B9780123852458000017 |access-date=18 April 2022 |chapter=Chapter 1 – Introduction to the Immune Response |archive-date=18 April 2022 |archive-url=https://web.archive.org/web/20220418192756/https://www.sciencedirect.com/science/article/pii/B9780123852458000017 |url-status=live }}</ref><ref name="Clem">{{cite journal |last1=Clem |first1=Angela S |title=Fundamentals of Vaccine Immunology |journal=Journal of Global Infectious Diseases |date=2011 |volume=3 |issue=1 |pages=73–78 |doi=10.4103/0974-777X.77299 |pmid=21572612 |pmc=3068582 |issn=0974-777X |doi-access=free }}</ref>

In 1958, there were 763,094 cases of measles in the United States; 552 deaths resulted.<ref name="pmid15106120">{{cite journal |vauthors=Orenstein WA, Papania MJ, Wharton ME |date=May 2004 |title=Measles elimination in the United States |journal=The Journal of Infectious Diseases |volume=189 |issue=Suppl 1 |pages=S1–3 |doi=10.1086/377693 |pmid=15106120 |doi-access=free}}</ref><ref name="pmid18463608">{{cite journal |vauthors=<!--staff--> |date=May 2008 |title=Measles – United States, January 1 – April 25, 2008 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5718a5.htm |url-status=live |journal=MMWR. Morbidity and Mortality Weekly Report |volume=57 |issue=18 |pages=494–498 |pmid=18463608 |archive-url=https://web.archive.org/web/20171011235122/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5718a5.htm |archive-date=11 October 2017}}</ref> After the introduction of new vaccines, the number of cases dropped to fewer than 150 per year (median of 56).<ref name="pmid18463608" /> In early 2008, there were 64 suspected cases of measles. Fifty-four of those infections were associated with importation from another country, although only thirteen percent were actually acquired outside the United States; 63 of the 64 individuals either had never been vaccinated against measles or were uncertain whether they had been vaccinated.<ref name="pmid18463608" />

The measles vaccine is estimated to prevent a million deaths every year.<ref name="sullivan2005">{{cite news |last=Sullivan |first=Patricia |name-list-style=vanc |date=13 April 2005 |title=Maurice R. Hilleman dies; created vaccines |url=https://www.washingtonpost.com/wp-dyn/articles/A48244-2005Apr12.html |url-status=live |archive-url=https://web.archive.org/web/20121020102622/http://www.washingtonpost.com/wp-dyn/articles/A48244-2005Apr12.html |archive-date=20 October 2012 |access-date=9 January 2014 |work=Wash. Post}}</ref>

Vaccines led to the eradication of [[smallpox]], one of the most contagious and deadly diseases in humans.<ref>{{cite web |title=Smallpox |url=https://www.who.int/csr/disease/smallpox/en/ |url-status=live |archive-url=https://web.archive.org/web/20070922184729/http://www.who.int/csr/disease/smallpox/en/ |archive-date=22 September 2007 |access-date=16 April 2019 |publisher=[[World Health Organization]] (WHO)}}</ref> Other diseases such as rubella, [[poliomyelitis|polio]], measles, mumps, [[chickenpox]], and [[typhoid fever|typhoid]] are nowhere near as common as they were a hundred years ago thanks to widespread vaccination programs. As long as the vast majority of people are vaccinated, it is much more difficult for an outbreak of disease to occur, let alone spread. This effect is called [[herd immunity]]. Polio, which is transmitted only among humans, is targeted by an extensive [[Poliomyelitis eradication|eradication campaign]] that has seen endemic polio restricted to only parts of three countries (Afghanistan, Nigeria, and Pakistan).<ref name="eradication1">{{cite web |date=27 March 2014 |title=WHO South-East Asia Region certified polio-free |url=http://www.searo.who.int/mediacentre/releases/2014/pr1569/en/ |archive-url=https://web.archive.org/web/20140327235218/http://www.searo.who.int/mediacentre/releases/2014/pr1569/en/ |archive-date=27 March 2014 |access-date=3 November 2014 |publisher=WHO}}</ref> However, the difficulty of reaching all children, cultural misunderstandings, and [[disinformation]] have caused the anticipated eradication date to be missed several times.<ref>{{cite web |date=21 May 2021 |title=Statement following the Twenty-Eighth IHR Emergency Committee for Polio |url=https://www.who.int/news/item/21-05-2021-statement-following-the-twenty-eighth-ihr-emergency-committee-for-polio |url-status=live |archive-url=https://web.archive.org/web/20220419014821/https://www.who.int/news/item/21-05-2021-statement-following-the-twenty-eighth-ihr-emergency-committee-for-polio |archive-date=19 April 2022 |access-date=19 April 2022 |website=[[World Health Organization]] (WHO)}}</ref><ref>{{cite journal |last1=Grassly |first1=Nicholas C. |date=5 August 2013 |title=The final stages of the global eradication of poliomyelitis |journal=Philosophical Transactions of the Royal Society B: Biological Sciences |volume=368 |issue=1623 |article-number=20120140 |doi=10.1098/rstb.2012.0140 |issn=0962-8436 |pmc=3720038 |pmid=23798688}}</ref><ref>{{cite journal |last1=Ittefaq |first1=Muhammad |last2=Abwao |first2=Mauryne |last3=Rafique |first3=Shanawer |date=3 August 2021 |title=Polio vaccine misinformation on social media: turning point in the fight against polio eradication in Pakistan |journal=Human Vaccines & Immunotherapeutics |volume=17 |issue=8 |pages=2575–2577 |doi=10.1080/21645515.2021.1894897 |issn=2164-554X |pmc=8475597 |pmid=33705246}}</ref><ref>{{cite news |date=24 January 2022 |title=Disinformation disturbs anti-polio drives |url=https://tribune.com.pk/story/2340158/disinformation-disturbs-anti-polio-drives |url-status=live |archive-url=https://web.archive.org/web/20220510052846/https://tribune.com.pk/story/2340158/disinformation-disturbs-anti-polio-drives |archive-date=10 May 2022 |access-date=19 April 2022 |work=The Express Tribune}}</ref>

Vaccines also help prevent the development of antibiotic resistance. For example, by greatly reducing the incidence of pneumonia caused by ''[[Streptococcus pneumoniae]]'', vaccine programs have greatly reduced the prevalence of infections resistant to penicillin or other first-line antibiotics.<ref>{{cite journal |last1=Abbott |first1=Alison |date=19 July 2017 |title=19 July 2017 ''Vaccines promoted as key to stamping out drug-resistant microbes'' "Immunization can stop resistant infections before they get started, say scientists from industry and academia." |url=https://www.nature.com/articles/d41586-017-01711-6 |journal=Nature |doi=10.1038/d41586-017-01711-6 |archive-url=https://web.archive.org/web/20170722121157/http://www.nature.com/articles/d41586-017-01711-6 |archive-date=22 July 2017|url-access=subscription }}</ref>

=== Limitations ===
Limitations to their effectiveness, nevertheless, exist.<ref name="pmid19393917">{{cite journal | vauthors = Grammatikos AP, Mantadakis E, Falagas ME | title = Meta-analyses on pediatric infections and vaccines | journal = Infectious Disease Clinics of North America | volume = 23 | issue = 2 | pages = 431–457 | date = June 2009 | pmid = 19393917 | doi = 10.1016/j.idc.2009.01.008 }}</ref> Sometimes, protection fails for vaccine-related reasons such as failures in vaccine attenuation, vaccination regimens or administration.<ref name="wied"/>

Failure may also occur for host-related reasons if the host's immune system does not respond adequately or at all. Host-related lack of response occurs in an estimated 2-10% of individuals, due to factors including genetics, immune status, age, health and nutritional status.<ref name="wied"/> One type of [[primary immunodeficiency]] disorder resulting in genetic failure is [[X-linked agammaglobulinemia]], in which the absence of an enzyme essential for [[B cell]] development prevents the host's immune system from generating [[Antibody|antibodies]] to a [[pathogen]].<ref>{{cite book |last1=Justiz Vaillant |first1=AA |last2=Ramphul |first2=K |title=Antibody Deficiency Disorder |location=Treasure Island, FL |publisher=StatPearls Publishing |date=January 2022 |pmid=29939682 |url=https://www.ncbi.nlm.nih.gov/books/NBK507905/ |access-date=18 April 2022}}</ref><ref name="Reda">{{cite journal |last1=Reda |first1=Shereen M. |last2=Cant |first2=Andrew J. |title=The importance of vaccination and immunoglobulin treatment for patients with primary immunodeficiency diseases (PIDs) – World PI Week April 22–29, 2015: FORUM |journal=European Journal of Immunology |date=May 2015 |volume=45 |issue=5 |pages=1285–1286 |doi=10.1002/eji.201570054 |pmid=25952627 |s2cid=1922332 }}</ref>

Host–pathogen interactions and responses to infection are dynamic processes involving multiple pathways in the immune system.<ref name="Jo">{{cite journal |last1=Jo |first1=Eun-Kyeong |title=Interplay between host and pathogen: immune defense and beyond |journal=Experimental & Molecular Medicine |date=December 2019 |volume=51 |issue=12 |pages=1–3 |doi=10.1038/s12276-019-0281-8 |pmid=31827066 |pmc=6906370 |issn=2092-6413}}</ref><ref name="Janeway">{{cite journal |last1=Janeway |first1=Charles A Jr. |last2=Travers |first2=Paul |last3=Walport |first3=Mark |last4=Shlomchik |first4=Mark J. |title=The Humoral Immune Response |journal=Immunobiology: The Immune System in Health and Disease|edition=5th |date=2001 |url=https://www.ncbi.nlm.nih.gov/books/NBK10752/ |access-date=18 April 2022 |archive-date=2 January 2021 |archive-url=https://web.archive.org/web/20210102142711/https://www.ncbi.nlm.nih.gov/books/NBK10752/ |url-status=live }}</ref> A host does not develop antibodies instantaneously: while the body's [[innate immunity]] may be activated in as little as twelve hours, [[adaptive immunity]] can take 1–2 weeks to fully develop. During that time, the host can still become infected.<ref>{{cite book |last1=Grubbs |first1=Hailey |last2=Kahwaji |first2=Chadi I. |title=Physiology, Active Immunity |location=Treasure Island, FL |publisher=StatPearls Publishing |date=January 2022 |pmid=29939682 |url=https://www.ncbi.nlm.nih.gov/books/NBK513280/ |access-date=18 April 2022 |archive-date=12 November 2021 |archive-url=https://web.archive.org/web/20211112145718/https://www.ncbi.nlm.nih.gov/books/NBK513280/ |url-status=live }}</ref>

Once antibodies are produced, they may promote immunity in any of several ways, depending on the class of antibodies involved. Their success in clearing or inactivating a pathogen will depend on the amount of antibodies produced and on the extent to which those antibodies are effective at countering the strain of the pathogen involved, since different strains may be differently susceptible to a given immune reaction.<ref name="Janeway"/> 
In some cases vaccines may result in partial immune protection (in which immunity is less than 100% effective but still reduces risk of infection) or in temporary immune protection (in which immunity wanes over time) rather than full or permanent immunity. They can still raise the reinfection threshold for the population as a whole and make a substantial impact.<ref name="Gomes">{{cite journal |last1=Gomes |first1=M. Gabriela M. |last2=White |first2=Lisa J. |last3=Medley |first3=Graham F. |title=Infection, reinfection, and vaccination under suboptimal immune protection: epidemiological perspectives |journal=Journal of Theoretical Biology |date=21 June 2004 |volume=228 |issue=4 |pages=539–549 |doi=10.1016/j.jtbi.2004.02.015 |pmid=15178201 |bibcode=2004JThBi.228..539G |hdl=10400.7/53 |hdl-access=free |issn=0022-5193}}</ref> They can also mitigate the severity of infection, resulting in a lower [[mortality rate]], lower [[morbidity]], faster recovery from illness, and a wide range of other effects.<ref name="Bonanni">{{cite journal |last1=Bonanni |first1=Paolo |last2=Picazo |first2=Juan José |last3=Rémy |first3=Vanessa |title=The intangible benefits of vaccination – what is the true economic value of vaccination? |journal=Journal of Market Access & Health Policy |date=12 August 2015 |volume=3 |article-number=10.3402/jmahp.v3.26964 |doi=10.3402/jmahp.v3.26964 |pmid=27123182 |pmc=4802696 |issn=2001-6689}}</ref><ref name="Stanciu">{{cite book |last1=Stanciu |first1=Stefan G. |title=Micro and Nanotechnologies for Biotechnology |year= 2016 |publisher=BoD – Books on Demand |isbn=978-953-51-2530-3 |url=https://books.google.com/books?id=h3eQDwAAQBAJ&pg=PA88 |access-date=19 April 2022 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114091817/https://books.google.com/books?id=h3eQDwAAQBAJ&pg=PA88 |url-status=live }}</ref>

Those who are older often display less of a response than those who are younger, a pattern known as [[Immunosenescence]].<ref name="Frasca">{{cite journal |last1=Frasca |first1=Daniela |last2=Diaz |first2=Alain |last3=Romero |first3=Maria |last4=Garcia |first4=Denisse |last5=Blomberg |first5=Bonnie B. |title=B Cell Immunosenescence |journal=Annual Review of Cell and Developmental Biology |date=6 October 2020 |volume=36 |issue=1 |pages=551–574 |doi=10.1146/annurev-cellbio-011620-034148 |pmid=33021823 |pmc=8060858 |issn=1081-0706}}</ref>
[[Immunologic adjuvant|Adjuvants]] commonly are used to boost immune response, particularly for older people whose immune response to a simple vaccine may have weakened.<ref name="neighmond2010">{{cite news | url=https://www.npr.org/templates/story/story.php?storyId=123406640 | title=Adapting Vaccines For Our Aging Immune Systems | date=7 February 2010 | work=Morning Edition | publisher=NPR | access-date=9 January 2014 | last=Neighmond | first=Patti | name-list-style = vanc | url-status=live | archive-url=https://web.archive.org/web/20131216191614/http://www.npr.org/templates/story/story.php?storyId=123406640 | archive-date=16 December 2013}}</ref>

The [[vaccine efficacy|efficacy]] or performance of the vaccine is dependent on several factors:
* the disease itself (for some diseases vaccination performs better than for others)
* the strain of vaccine (some vaccines are specific to, or at least most effective against, particular strains of the disease)<ref name="pmid10435956">{{cite journal | vauthors = Schlegel M, Osterwalder JJ, Galeazzi RL, Vernazza PL | title = Comparative efficacy of three mumps vaccines during disease outbreak in Eastern Switzerland: cohort study | journal = BMJ | volume = 319 | issue = 7206 | page = 352 | date = August 1999 | pmid = 10435956 | pmc = 32261 | doi = 10.1136/bmj.319.7206.352 }}</ref>
* whether the [[vaccination schedule]] has been properly observed.
* idiosyncratic response to vaccination; some individuals are "non-responders" to certain vaccines, meaning that they do not generate antibodies even after being vaccinated correctly.
* assorted factors such as ethnicity, age, or genetic predisposition.

If a vaccinated individual does develop the disease vaccinated against ([[breakthrough infection]]), the disease is likely to be less severe and less transmissible than in unvaccinated cases.<ref name="pmid12955637">{{cite journal | vauthors = Préziosi MP, Halloran ME | title = Effects of pertussis vaccination on disease: vaccine efficacy in reducing clinical severity | journal = Clinical Infectious Diseases | volume = 37 | issue = 6 | pages = 772–779 | date = September 2003 | pmid = 12955637 | doi = 10.1086/377270 | doi-access = free }}</ref><ref>{{Cite journal |last1=Connell |first1=Anna R. |last2=Connell |first2=Jeff |last3=Leahy |first3=T. Ronan |last4=Hassan |first4=Jaythoon |date=2020-09-18 |title=Mumps Outbreaks in Vaccinated Populations – Is It Time to Re-assess the Clinical Efficacy of Vaccines? |journal=Frontiers in Immunology |language=English |volume=11 |page=2089 |doi=10.3389/fimmu.2020.02089 |doi-access=free |issn=1664-3224 |pmc=7531022 |pmid=33072071}}</ref>

Important considerations in an effective vaccination program:<ref>{{Cite journal|last1=Miller|first1=E.|last2=Beverley|first2=P. C. L.|last3=Salisbury|first3=D. M.|date=1 July 2002|title=Vaccine programmes and policies|journal=British Medical Bulletin|volume=62|issue=1|pages=201–211|doi=10.1093/bmb/62.1.201|pmid=12176861|issn=0007-1420|doi-access=free}}</ref>
# careful modeling to anticipate the effect that an immunization campaign will have on the epidemiology of the disease in the medium to long term
# ongoing surveillance for the relevant disease following introduction of a new vaccine
# maintenance of high immunization rates, even when a disease has become rare

== Safety ==
{{main|Adverse vaccine event}}
Vaccinations given to children, adolescents, or adults are generally safe.<ref>{{Cite journal|last1=Dudley|first1=Matthew Z|last2=Halsey|first2=Neal A|last3=Omer|first3=Saad B|last4=Orenstein|first4=Walter A|last5=O'Leary|first5=Sean T|last6=Limaye|first6=Rupali J|last7=Salmon|first7=Daniel A|date=May 2020|title=The state of vaccine safety science: systematic reviews of the evidence |journal=The Lancet Infectious Diseases|volume=20|issue=5|pages=e80–e89|doi=10.1016/s1473-3099(20)30130-4|pmid=32278359|s2cid=215751248|issn=1473-3099}}</ref><ref name=Mag2014>{{cite journal | vauthors = Maglione MA, Das L, Raaen L, Smith A, Chari R, Newberry S, Shanman R, Perry T, Goetz MB, Gidengil C | title = Safety of vaccines used for routine immunization of U.S. children: a systematic review | journal = Pediatrics | volume = 134 | issue = 2 | pages = 325–337 | date = August 2014 | pmid = 25086160 | doi = 10.1542/peds.2014-1079 | url = http://www.escholarship.org/uc/item/2f93s53t | doi-access = free | access-date = 1 July 2019 | archive-date = 30 January 2020 | archive-url = https://web.archive.org/web/20200130171937/https://escholarship.org/uc/item/2f93s53t | url-status = live }}</ref> Adverse effects, if any, are generally mild.<ref name=CDC2013>{{cite web|title=Possible Side-effects from Vaccines|url=https://www.cdc.gov/vaccines/vac-gen/side-effects.htm|work=Centers for Disease Control and Prevention|access-date=24 February 2014|url-status=live|archive-url=https://web.archive.org/web/20170317050028/https://www.cdc.gov/vaccines/vac-gen/side-effects.htm|archive-date=17 March 2017|date=12 July 2018}}</ref> The rate of side effects depends on the vaccine in question.<ref name=CDC2013/> Some common side effects include fever, pain around the injection site, and muscle aches.<ref name=CDC2013/> Additionally, some individuals may be allergic to ingredients in the vaccine.<ref>{{cite web|url=https://www.cdc.gov/flu/about/qa/flushot.htm|title=Seasonal Flu Shot – Seasonal Influenza |publisher=CDC|archive-url=https://web.archive.org/web/20151001040007/http://www.cdc.gov/flu/about/qa/flushot.htm|archive-date=1 October 2015|date=2 October 2018|access-date=17 September 2017}}</ref> The [[MMR vaccine]] is rarely associated with [[febrile seizure]]s.<ref name=Mag2014/>

Host-("vaccinee")-related determinants that render a person susceptible to infection, such as [[genetics]], health status (underlying disease, nutrition, pregnancy, [[Hypersensitivity|sensitivities]] or [[Allergy|allergies]]), [[Immunocompetence|immune competence]], age, and [[Economic impact of the COVID-19 pandemic|economic impact]] or [[Synthetic psychological environment|cultural environment]] can be primary or secondary factors affecting the severity of infection and response to a vaccine.<ref name="wied">{{Cite journal|last1=Wiedermann|first1=Ursula|last2=Garner-Spitzer|first2=Erika|last3=Wagner|first3=Angelika|year=2016|title=Primary vaccine failure to routine vaccines: Why and what to do?|journal=Human Vaccines & Immunotherapeutics|volume=12|issue=1|pages=239–243|doi=10.1080/21645515.2015.1093263|issn=2164-554X|pmc=4962729|pmid=26836329|name-list-style=vanc}}</ref> Elderly (above age 60), [[Type I hypersensitivity|allergen-hypersensitive]], and [[Obesity|obese]] people have susceptibility to compromised [[immunogenicity]], which prevents or inhibits vaccine effectiveness, possibly requiring separate vaccine technologies for these specific populations or repetitive [[Booster dose|booster vaccinations]] to limit [[Transmission (medicine)|virus transmission]].<ref name="wied" />

Severe side effects are extremely rare.<ref name=Mag2014/> [[Varicella vaccine]] is rarely associated with complications in [[immunodeficient]] individuals, and [[rotavirus vaccine]]s are moderately associated with [[intussusception (medical disorder)|intussusception]].<ref name=Mag2014/>

At least 19 countries have no-fault compensation programs to provide compensation for those with severe adverse effects of vaccination.<ref>{{cite journal |last1=Looker |first1=Clare|last2= Heath|first2= Kelly | name-list-style = vanc |title=No-fault compensation following adverse events attributed to vaccination: a review of international programmes |journal=Bulletin of the World Health Organization|year=2011 |volume=89|issue=5|pages=371–378|url=https://www.who.int/bulletin/volumes/89/5/10-081901/en/ |archive-url=https://web.archive.org/web/20130811171023/http://www.who.int/bulletin/volumes/89/5/10-081901/en/ |archive-date=11 August 2013 |publisher=Word Health Organisation|doi=10.2471/BLT.10.081901|pmid=21556305|pmc=3089384}}</ref> The United States' program is known as the [[National Childhood Vaccine Injury Act]], and the United Kingdom employs the [[Vaccine Damage Payment]].

==Types==
[[File:WHO EN Vaccines Topics Race for a COVID-19 vaccine 01 12Jan2021.jpg|thumb|alt=Illustration with the text "There are three main approaches to making a vaccine: Using a whole virus or bacterium Parts that trigger the immune system Just the genetic material."|<!--[[wp:caption]] "Not every image ..."-->]]
Vaccines typically contain attenuated, inactivated or dead organisms or purified products derived from them. There are several types of vaccines in use.<ref>{{cite web|url = https://www.niaid.nih.gov/topics/vaccines/Pages/typesVaccines.aspx|title = Vaccine Types|publisher = [[NIAID|National Institute of Allergy and Infectious Diseases]]|date = 3 April 2012|access-date = 27 January 2015|url-status=dead|archive-url = https://web.archive.org/web/20150905205720/http://www.niaid.nih.gov/topics/vaccines/Pages/typesVaccines.aspx%7C|archive-date = 5 September 2015}}</ref> These represent different strategies used to try to reduce the risk of illness while retaining the ability to induce a beneficial immune response.

===Attenuated===
{{main|Attenuated vaccine}}

Some vaccines contain live, [[attenuated vaccine|attenuated]] microorganisms. Many of these are active [[viruses]] that have been cultivated under conditions that disable their virulent properties, or that use closely related but less dangerous organisms to produce a broad immune response. Although most attenuated vaccines are viral, some are bacterial in nature. Examples include the viral diseases [[yellow fever]], [[measles]], [[mumps]], and [[rubella]], and the bacterial disease [[typhoid]]. The live ''Mycobacterium [[tuberculosis]]'' vaccine developed by Calmette and Guérin is not made of a [[Infectious disease|contagious]] strain but contains a virulently modified strain called "[[Bacillus Calmette-Guérin|BCG]]" used to elicit an immune response to the vaccine. The live attenuated vaccine containing strain ''[[Yersinia pestis]]'' EV is used for [[Plague (disease)|plague]] immunization. Attenuated vaccines have some advantages and disadvantages. Attenuated, or live, weakened, vaccines typically provoke more durable immunological responses. Attenuated vaccines also elicit a cellular and humoral response. However, they may not be safe for use in immunocompromised individuals, and on rare occasions mutate to a virulent form and cause disease.<ref name="Bhattacharya">{{cite book | vauthors = Sinha JK, Bhattacharya S | title=A Text Book of Immunology | url=https://books.google.com/books?id=ytCNCbCWx8oC&pg=PA318 | format=Google Books Preview | publisher=Academic Publishers | isbn=978-81-89781-09-5 | page=318 | access-date=9 January 2014}}</ref>

===Inactivated===
{{main|Inactivated vaccine}}

Some vaccines contain microorganisms that have been killed or inactivated by physical or chemical means. Examples include IPV ([[polio vaccine]]), [[hepatitis&nbsp;A vaccine]], [[rabies vaccine]] and most [[influenza vaccines]].<ref>{{cite web|url=https://www.vaccines.gov/basics/types/index.html|title=Types of Vaccines |archive-url=https://web.archive.org/web/20170729161636/https://www.vaccines.gov/basics/types/index.html|archive-date=29 July 2017|url-status=live|access-date=19 October 2017}}</ref><ref name="historyofvaccines.org">{{cite web|url=https://www.historyofvaccines.org/content/articles/different-types-vaccines|title=Different Types of Vaccines |website=History of Vaccines |access-date=14 June 2019|archive-date=26 January 2019|archive-url=https://web.archive.org/web/20190126060918/https://www.historyofvaccines.org/content/articles/different-types-vaccines|url-status=live}}</ref>[[File:ReverseGeneticsFlu.svg|thumbnail|300px|[[Avian influenza|Avian flu]] vaccine development by [[reverse genetics]] techniques]]

===Toxoid===
{{main|Toxoid}}

[[Toxoid]] vaccines are made from inactivated toxic compounds that cause illness rather than the microorganism.<ref name="historyofvaccines.org"/> Examples of toxoid-based vaccines include [[tetanus]] and [[diphtheria]].<ref name="historyofvaccines.org" /> Not all toxoids are for microorganisms; for example, ''[[Crotalus atrox]]'' toxoid is used to vaccinate dogs against [[rattlesnake]] bites.<ref>{{cite web|url=http://coastalcarolinaresearch.com/types-of-vaccines/|title=Types of Vaccines|website=coastalcarolinaresearch.com|access-date=3 May 2019|archive-date=3 May 2019|archive-url=https://web.archive.org/web/20190503112746/http://coastalcarolinaresearch.com/types-of-vaccines/}}</ref>

===Subunit===
{{main|Subunit vaccine}}

Rather than introducing an inactivated or attenuated microorganism to an immune system (which would constitute a "whole-agent" vaccine), a [[Protein subunit|subunit]] vaccine uses a fragment of it to create an immune response. One example is the subunit vaccine against [[Hepatitis B#Virology|hepatitis{{spaces}}B]], which is composed of only the surface proteins of the virus (previously extracted from the [[blood serum]] of chronically infected patients but now produced by [[recombinant DNA|recombination]] of the viral genes into [[yeast]]).<ref>{{cite web|url=https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-details/vaccine-hepatitis-b-vaccine|title=A Look at Each Vaccine: Hepatitis B Vaccine|last=Philadelphia|first=The Children's Hospital of|date=18 August 2014|website=www.chop.edu|access-date=14 June 2019|archive-date=31 May 2019|archive-url=https://web.archive.org/web/20190531160201/https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-details/vaccine-hepatitis-b-vaccine|url-status=live}}</ref> Other examples include the [[Gardasil]] [[virus-like particle]] [[human papillomavirus]] (HPV) vaccine,<ref>{{cite web|url=https://www.cdc.gov/vaccines/vpd/hpv/hcp/vaccines.html|title=HPV Vaccine {{!}} Human Papillomavirus {{!}} CDC|date=13 May 2019|website=www.cdc.gov|access-date=14 June 2019|archive-date=18 June 2019|archive-url=https://web.archive.org/web/20190618034022/https://www.cdc.gov/vaccines/vpd/hpv/hcp/vaccines.html|url-status=live}}</ref> the [[hemagglutinin]] and [[neuraminidase]] subunits of the [[influenza]] virus,<ref name="historyofvaccines.org"/> and [[edible algae vaccine]]s. A subunit vaccine is being used for plague immunization.<ref>{{Cite journal|last1=Williamson|first1=E. D.|last2=Eley|first2=S. M.|last3=Griffin|first3=K. F.|last4=Green|first4=M.|last5=Russell|first5=P.|last6=Leary|first6=S. E.|last7=Oyston|first7=P. C.|last8=Easterbrook|first8=T.|last9=Reddin|first9=K. M.|date=December 1995|title=A new improved sub-unit vaccine for plague: the basis of protection|journal=FEMS Immunology and Medical Microbiology|volume=12|issue=3–4|pages=223–230|doi=10.1111/j.1574-695X.1995.tb00196.x|issn=0928-8244|pmid=8745007|doi-access=free}}</ref>

===Conjugate===
{{main|Conjugate vaccine}}

Certain bacteria have a polysaccharide [[Bacterial capsule|outer coat]] that is poorly [[immunogenic]]. By linking these outer coats to proteins (e.g., toxins), the [[immune system]] can be led to recognize the [[polysaccharide]] as if it were a protein antigen. This approach is used in the [[Hib vaccine|''Haemophilus influenzae'' type B vaccine]].<ref>{{cite web|url=http://www.globalhealthprimer.emory.edu/targets-technologies/polysaccharide-protein-conjugate-vaccines.html|title=Polysaccharide Protein Conjugate Vaccines|website=www.globalhealthprimer.emory.edu|access-date=14 June 2019|archive-date=23 June 2019|archive-url=https://web.archive.org/web/20190623043558/http://www.globalhealthprimer.emory.edu/targets-technologies/polysaccharide-protein-conjugate-vaccines.html|url-status=live}}</ref>

===Outer membrane vesicle===

[[Bacterial outer membrane vesicles|Outer membrane vesicles]] (OMVs) are naturally immunogenic and can be manipulated to produce potent vaccines. The best known OMV vaccines are those developed for [[Meningococcal vaccine#Serogroup B|serotype B meningococcal disease]].<ref name="vaccinology-guide">{{cite journal |vauthors=Pollard AJ, Bijker EM |title=A guide to vaccinology: from basic principles to new developments |journal=Nature Reviews Immunology |date=22 December 2020 |volume=21 |issue=2 |pages=83–100 |doi=10.1038/s41577-020-00479-7 |pmid=33353987 |pmc=7754704 |issn=1474-1741 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Pol L, Stork M, Ley P |date=11 November 2015 |title=Outer membrane vesicles as platform vaccine technology |journal=Biotechnology Journal |volume=10 |issue=11 |pages=1689–1706 |doi=10.1002/biot.201400395 |issn=1860-7314 |pmc=4768646 |pmid=26912077 }}</ref>

===Heterotypic===
{{main|Heterologous vaccine}}

[[Heterologous vaccine]]s also known as "Jennerian vaccines", are vaccines that are pathogens of other animals that either do not cause disease or cause mild disease in the organism being treated. The classic example is Jenner's use of cowpox to protect against smallpox. A current example is the use of [[BCG vaccine]] made from ''[[Mycobacterium bovis]]'' to protect against [[tuberculosis]].<ref>{{cite journal|last=Scott|date=April 2004|title=Classifying Vaccines|url=http://www.bioprocessintl.com/multimedia/archive/00077/0204su03_77445a.pdf|url-status=live|journal=BioProcesses International|pages=14–23|archive-url=https://web.archive.org/web/20131212222400/http://www.bioprocessintl.com/multimedia/archive/00077/0204su03_77445a.pdf|archive-date=12 December 2013|access-date=9 January 2014}}</ref>

=== Genetic vaccine ===
{{main|Genetic vaccine}}

Genetic vaccines are based on the principle of uptake of a nucleic acid into cells, whereupon a protein is produced according to the nucleic acid template. This protein is usually the immunodominant antigen of the pathogen or a surface protein that enables the formation of neutralizing antibodies. The subgroup of genetic vaccines encompass viral vector vaccines, RNA vaccines and DNA vaccines.{{citation needed|date=January 2024}}

==== Viral vector ====
{{main|Viral vector vaccine}}

Viral vector vaccines use a safe [[virus]] to insert pathogen genes in the body to produce specific [[antigen]]s, such as surface [[protein]]s, to stimulate an [[immune response]].<ref>{{cite web |url=https://www.vaccines.gov/basics/types |title=Vaccine Types |website=Vaccines.org |publisher=Office of Infectious Disease of the [[United States Department of Health and Human Services]] |access-date=13 March 2021 |archive-date=23 May 2019 |archive-url=https://web.archive.org/web/20190523191043/https://www.vaccines.gov/basics/types |url-status=live }}</ref><ref>{{cite web |url=https://www.cdc.gov/vaccines/covid-19/hcp/viral-vector-vaccine-basics.html |title=Understanding and Explaining Viral Vector COVID-19 Vaccines |publisher=[[Centers for Disease Control and Prevention]] |access-date=13 March 2021 |archive-date=2 February 2021 |archive-url=https://web.archive.org/web/20210202160930/https://www.cdc.gov/vaccines/covid-19/hcp/viral-vector-vaccine-basics.html |url-status=live }}</ref> Viruses being researched for use as viral vectors include adenovirus, vaccinia virus, and [[Indiana vesiculovirus|VSV]].

====RNA====
{{main|RNA vaccine}}

An mRNA vaccine (or [[RNA vaccine]]) is a novel type of vaccine which is composed of the nucleic acid RNA, packaged within a vector such as lipid [[nanoparticle]]s.<ref>{{cite web | last1=Garde | first1=Damian | last2=Feuerstein | first2=Adam | title=How nanotechnology helps mRNA Covid-19 vaccines work | website=STAT | date=1 November 2020 | url=https://www.statnews.com/2020/12/01/how-nanotechnology-helps-mrna-covid19-vaccines-work/ | access-date=21 December 2020 | archive-date=1 December 2020 | archive-url=https://web.archive.org/web/20201201210905/https://www.statnews.com/2020/12/01/how-nanotechnology-helps-mrna-covid19-vaccines-work/ | url-status=live }}</ref> Among the [[COVID-19 vaccine]]s are a number of RNA vaccines to combat the [[COVID-19 pandemic]] and some have been approved or have received [[emergency use authorization]] in some countries. For example, the [[Pfizer–BioNTech COVID-19 vaccine|Pfizer-BioNTech]] vaccine and [[Moderna COVID-19 vaccine|Moderna mRNA]] vaccine are approved for use in adults and children in the US.<ref>{{cite web | author=CDC | title=COVID-19 and Your Health | website=Centers for Disease Control and Prevention | date=11 February 2020 | url=https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html | access-date=21 December 2020 | archive-date=3 March 2021 | archive-url=https://web.archive.org/web/20210303003047/https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html | url-status=live }}</ref><ref>{{cite web | last=Banks | first=Marcus A. | title=What Are mRNA Vaccines, and Could They Work Against COVID-19? | website=Smithsonian Magazine | date=16 July 2020 | url=https://www.smithsonianmag.com/science-nature/mrna-vaccines-covid-19-180975330/ | access-date=21 December 2020 | archive-date=21 December 2020 | archive-url=https://web.archive.org/web/20201221010102/https://www.smithsonianmag.com/science-nature/mrna-vaccines-covid-19-180975330/ | url-status=live }}</ref><ref>{{cite web | last=Branswell | first=Helen | title=FDA grants authorization to Moderna's Covid-19 vaccine | website=STAT | date=19 December 2020 | url=https://www.statnews.com/2020/12/18/fda-eua-moderna-vaccine-covid19/ | access-date=21 December 2020 | archive-date=21 December 2020 | archive-url=https://web.archive.org/web/20201221163920/https://www.statnews.com/2020/12/18/fda-eua-moderna-vaccine-covid19/ | url-status=live }}</ref>

====DNA====
{{main|DNA vaccine}}

A DNA vaccine uses a [[DNA]] [[plasmid]] (pDNA)) that encodes for an antigenic protein originating from the pathogen upon which the vaccine will be targeted. pDNA is inexpensive, stable, and relatively safe, making it an excellent option for vaccine delivery.<ref>{{Cite web |last=Cuffari |first=Benedette |date=17 March 2021 |title=What is a DNA Vaccine? |url=https://www.news-medical.net/health/What-is-a-DNA-based-vaccine.aspx |access-date=14 January 2024 |website=News-Medical.net |archive-date=14 January 2024 |archive-url=https://web.archive.org/web/20240114104703/https://www.news-medical.net/health/What-is-a-DNA-based-vaccine.aspx |url-status=live }}</ref>

This approach offers a number of potential advantages over traditional approaches, including the stimulation of both B- and T-cell responses, improved vaccine stability, the absence of any infectious agent and the relative ease of large-scale manufacture.<ref>{{Cite web |title=DNA Vaccines |url=https://www.who.int/teams/health-product-policy-and-standards/standards-and-specifications/vaccines-quality/dna |access-date=14 January 2024 |website=[[World Health Organization]] (WHO) |archive-date=14 January 2024 |archive-url=https://web.archive.org/web/20240114104704/https://www.who.int/teams/health-product-policy-and-standards/standards-and-specifications/vaccines-quality/dna |url-status=live }}</ref>

===Experimental===
Many innovative vaccines are also in development and use.
* Dendritic cell vaccines combine [[dendritic cell]]s with antigens to present the antigens to the body's white blood cells, thus stimulating an immune reaction. These vaccines have shown some positive preliminary results for treating brain tumors<ref>{{cite journal | vauthors = Kim W, Liau LM | title = Dendritic cell vaccines for brain tumors | journal = Neurosurgery Clinics of North America | volume = 21 | issue = 1 | pages = 139–157 | date = January 2010 | pmid = 19944973 | pmc = 2810429 | doi = 10.1016/j.nec.2009.09.005 }}</ref> and are also tested in malignant melanoma.<ref name="pmid24872109">{{cite journal | vauthors = Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN | title = Clinical use of dendritic cells for cancer therapy | journal = The Lancet. Oncology | volume = 15 | issue = 7 | pages = e257–267 | date = June 2014 | pmid = 24872109 | doi = 10.1016/S1470-2045(13)70585-0 }}</ref>
* [[Recombinant DNA|Recombinant]] [[Viral vector vaccine|vector]]{{snd}}by combining the physiology of one microorganism and the [[DNA]] of another, immunity can be created against diseases that have complex infection processes. An example is the [[RVSV-ZEBOV vaccine]] licensed to Merck that is being used in 2018 to combat [[2017 Democratic Republic of the Congo Ebola virus outbreak|ebola in Congo]].<ref>{{cite news|last1=McKenzie|first1=David|title=Fear and failure: How Ebola sparked a global health revolution|url=https://edition.cnn.com/2018/05/26/health/ebola-outbreaks-west-africa-congo-revolution-mckenzie-intl/index.html|access-date=26 May 2018|publisher=CNN|date=26 May 2018|archive-date=26 August 2019|archive-url=https://web.archive.org/web/20190826101345/https://edition.cnn.com/2018/05/26/health/ebola-outbreaks-west-africa-congo-revolution-mckenzie-intl/index.html|url-status=live}}</ref>
* [[T-cell receptor]] peptide vaccines are under development for several diseases using models of [[Valley Fever]], [[stomatitis]], and [[atopic dermatitis]]. These peptides have been shown to modulate [[cytokine]] production and improve cell-mediated immunity.
* Targeting of identified bacterial proteins that are involved in complement inhibition would neutralize the key bacterial virulence mechanism.<ref name="pmid19388175">{{cite journal | vauthors = Meri S, Jördens M, Jarva H | title = Microbial complement inhibitors as vaccines | journal = Vaccine | volume = 26 | pages = I113–117 | date = December 2008 | issue = Suppl 8 | pmid = 19388175 | doi = 10.1016/j.vaccine.2008.11.058 }}</ref>
* The use of [[plasmid]]s has been validated in preclinical studies as a protective vaccine strategy for cancer and infectious diseases. However, in human studies, this approach has failed to provide clinically relevant benefit. The overall efficacy of plasmid DNA immunization depends on increasing the plasmid's [[immunogenicity]] while also correcting for factors involved in the specific activation of immune effector cells.<ref name="Lowe">{{cite book|author=Lowe|title=Plasmids: Current Research and Future Trends|publisher=Caister Academic Press|year=2008|isbn=978-1-904455-35-6|chapter=Plasmid DNA as Prophylactic and Therapeutic vaccines for Cancer and Infectious Diseases|chapter-url=http://www.horizonpress.com/pla|access-date=15 April 2008|archive-date=11 April 2008|archive-url=https://web.archive.org/web/20080411053922/http://www.horizonpress.com/pla|url-status=live}}</ref>
* [[Vector (epidemiology)|Bacterial vector]] – Similar in principle to [[viral vector vaccine]]s, but using bacteria instead.<ref name="vaccinology-guide"/>
* [[Antigen-presenting cell vaccine|Antigen-presenting cell]]<ref name="vaccinology-guide"/>
* Technologies which may allow rapid vaccine deployment in response to a [[Emerging infectious disease|novel pathogen]] include the use of [[virus-like particle]]s<ref>{{Cite web |last1=Chang |first1=Lee-Jah |last2=Blair |first2=Wade |date=11 December 2023 |title=Mimicking nature: Virus-like particles and the next generation of vaccines |url=https://www.astrazeneca.com/what-science-can-do/topics/technologies/virus-like-particles-next-generation-vaccines.html |website=AstraZeneca}}</ref> or protein nanoparticles.<ref>{{Cite web |last=Cambridge |first=University of |title='Quartet Nanocage' vaccine found effective against coronaviruses that haven't even emerged yet |url=https://phys.org/news/2024-05-quartet-nanocage-vaccine-effective-coronaviruses.html |access-date=6 May 2024 |website=phys.org }}</ref>
* [[Inverse vaccine]]s are vaccines that train the immune system to not respond to certain substances.

While most vaccines are created using inactivated or attenuated compounds from microorganisms, [[synthetic vaccine]]s are composed mainly or wholly of synthetic peptides, carbohydrates, or antigens.{{Citation needed|date=May 2024}}

==Valence==
Vaccines may be ''monovalent'' (also called ''univalent'') or ''multivalent'' (also called ''polyvalent''). A monovalent vaccine is designed to immunize against a single antigen or single microorganism.<ref>{{DorlandsDict|five/000067458.htm|Monovalent}}</ref> A multivalent or polyvalent vaccine is designed to immunize against two or more strains of the same microorganism, or against two or more microorganisms.<ref>{{cite web |url=http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSz000113928zPzhtm |title=Polyvalent vaccine |website=[[Dorland's medical reference works|Dorland's Medical Dictionary]] |date=7 March 2012 |archive-url=https://web.archive.org/web/20120307130121/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSz000113928zPzhtm |archive-date=7 March 2012 }}</ref> The valency of a multivalent vaccine may be denoted with a Greek or Latin prefix (e.g., ''bivalent'', ''trivalent'', or ''tetravalent/quadrivalent''). In certain cases, a monovalent vaccine may be preferable for rapidly developing a strong immune response.<ref>{{Cite journal |url=http://www.pediatriconcall.com/fordoctor/Medical_original_articles/oral_polio_vaccine.asp |title=Questions And Answers On Monovalent Oral Polio Vaccine Type 1 (mOPV1) 'Issued Jointly By WHO and UNICEF' |date=8 January 2005<!--last update--> |journal=[[Pediatric Oncall]] |volume=2 |issue=8 |archive-url=https://web.archive.org/web/20120229143829/http://www.pediatriconcall.com/fordoctor/medical_original_articles/oral_polio_vaccine.asp |archive-date=29 February 2012 |at=3. What advantages does mOPV1 have over trivalent oral polio vaccine (tOPV)?}}</ref>

=== Interactions ===
When two or more vaccines are mixed in the same formulation, the two vaccines can interfere. This most frequently occurs with live attenuated vaccines, where one of the vaccine components is more robust than the others and suppresses the growth and immune response to the other components.<ref>{{cite journal |last1=Gizurarson |first1=Sveinbj??rn |title=Clinically Relevant Vaccine-Vaccine Interactions: A Guide for Practitioners |journal=BioDrugs |date=1998 |volume=9 |issue=6 |pages=443–453 |doi=10.2165/00063030-199809060-00002|pmid=18020577 |doi-access=free }}</ref>

This phenomenon was noted in the trivalent Sabin [[polio vaccine]], where the relative amount of serotype{{spaces}}2 virus in the vaccine had to be reduced to stop it from interfering with the "take" of the serotype{{spaces}}1 and{{spaces}}3 viruses in the vaccine. To accomplish this, the doses of serotypes{{spaces}}1 and{{spaces}}3 were increased in the vaccine in the early 1960s.<ref>{{cite book |title=Vaccines: Expert Consult (Vaccines (Plotkin)) |vauthors=Sutter RW, Kew OM, Cochi SL |publisher=W. B. Saunders |year=2008 |veditors=Orenstein WA, Offit PA, Plotkin SA |location= |page=650 |chapter=Poliovirus vaccine-live |isbn=978-1416036111}}</ref> It was also noted in a 2001 study to be a problem with [[dengue]] vaccines, where the DEN-3 serotype was found to predominate and suppress the response to DEN-1, -2 and -4 serotypes.<ref>{{cite journal |vauthors=Kanesa-thasan N, Sun W, Kim-Ahn G, Van Albert S, Putnak JR, King A, Raengsakulsrach B, Christ-Schmidt H, Gilson K, Zahradnik JM, Vaughn DW, Innis BL, Saluzzo JF, Hoke CH |date=April 2001 |title=Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers |journal=Vaccine |volume=19 |issue=23–24 |pages=3179–3188 |citeseerx=10.1.1.559.8311 |doi=10.1016/S0264-410X(01)00020-2 |pmid=11312014}}</ref>

==Other contents==
{{Excerpt|Vaccine ingredients}}

===Adjuvants===
{{main|Immunologic adjuvant}}

Vaccines typically contain one or more [[adjuvant]]s, used to boost the immune response. Tetanus toxoid, for instance, is usually adsorbed onto [[alum]]. This presents the antigen in such a way as to produce a greater action than the simple aqueous tetanus toxoid. People who have an adverse reaction to adsorbed tetanus toxoid may be given the simple vaccine when the time comes for a booster.<ref>{{Cite journal|last1=Engler|first1=Renata J. M.|last2=Greenwood|first2=John T.|last3=Pittman|first3=Phillip R.|last4=Grabenstein|first4=John D.|date=1 August 2006|title=Immunization to Protect the US Armed Forces: Heritage, Current Practice, and Prospects|journal=Epidemiologic Reviews|volume=28|issue=1|pages=3–26|doi=10.1093/epirev/mxj003|issn=0193-936X|pmid=16763072|doi-access=free}}</ref>

In the preparation for the 1990 Persian Gulf campaign, the whole cell [[pertussis]] vaccine was used as an adjuvant for [[anthrax]] vaccine. This produces a more rapid immune response than giving only the anthrax vaccine, which is of some benefit if exposure might be imminent.<ref>{{Cite book|last1=Sox|first1=Harold C.|url=https://www.ncbi.nlm.nih.gov/books/NBK222854/|title=Vaccines|last2=Liverman|first2=Catharyn T.|last3=Fulco|first3=Carolyn E.|last4=War|first4=Institute of Medicine (US) Committee on Health Effects Associated with Exposures During the Gulf|date=2000|publisher=National Academies Press (US)|access-date=3 May 2019|archive-date=16 November 2021|archive-url=https://web.archive.org/web/20211116025125/https://www.ncbi.nlm.nih.gov/books/NBK222854/|url-status=live}}</ref>

===Preservatives===
Vaccines may also contain preservatives to prevent contamination with [[bacteria]] or [[fungi]]. Until recent years, the preservative [[thiomersal]] ({{a.k.a.}} ''Thimerosal'' in the US and Japan) was used in many vaccines that did not contain live viruses. As of 2005, the only childhood vaccine in the U.S. that contains thiomersal in greater than trace amounts is the influenza vaccine,<ref>{{cite web|title=Institute for Vaccine Safety – Thimerosal Table|url=http://www.vaccinesafety.edu/thi-table.htm|url-status=live|archive-url=https://web.archive.org/web/20051210210622/http://www.vaccinesafety.edu/thi-table.htm|archive-date=10 December 2005}}</ref> which is currently recommended only for children with certain risk factors.<ref>Wharton, Melinda E.; National Vaccine Advisory committee [https://www.hhs.gov/nvpo/vacc_plan/ "U.S.A. national vaccine plan"] {{webarchive|url=https://web.archive.org/web/20160504053302/http://www.hhs.gov/nvpo/vacc_plan|date=4 May 2016}}</ref> Single-dose influenza vaccines supplied in the UK do not list thiomersal in the ingredients. Preservatives may be used at various stages of the production of vaccines, and the most sophisticated methods of measurement might detect traces of them in the finished product, as they may in the environment and population as a whole.<ref>{{cite web|title=Measurements of Non-gaseous air pollutants > Metals|url=http://www.npl.co.uk/environment/vam/nongaseouspollutants/ngp_metals.html|archive-url=https://web.archive.org/web/20070929124159/http://www.npl.co.uk/environment/vam/nongaseouspollutants/ngp_metals.html|archive-date=29 September 2007|access-date=28 June 2020|website=npl.co.uk|publisher=National Physics Laboratory}}</ref>

Many vaccines need preservatives to prevent serious adverse effects such as ''[[Staphylococcus]]'' infection, which in one 1928 incident killed 12 of 21 children inoculated with a [[diphtheria]] vaccine that lacked a preservative.<ref>{{cite web|date=6 September 2007|title=Thimerosal in vaccines|url=https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/UCM096228|url-status=dead|archive-url=https://web.archive.org/web/20130106215029/https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/UCM096228|archive-date=6 January 2013|access-date=1 October 2007|publisher=Center for Biologics Evaluation and Research, U.S. Food and Drug Administration}}</ref> Several preservatives are available, including thiomersal, [[phenoxyethanol]], and [[formaldehyde]]. Thiomersal is more effective against bacteria, has a better shelf-life, and improves vaccine stability, potency, and safety; however, in the U.S., the [[European Union]], and a few other affluent countries, it is no longer used as a preservative in childhood vaccines, as a precautionary measure due to its [[Mercury (element)|mercury]] content.<ref>{{cite journal|vauthors=Bigham M, Copes R|year=2005|title=Thiomersal in vaccines: balancing the risk of adverse effects with the risk of vaccine-preventable disease|journal=Drug Safety|volume=28|issue=2|pages=89–101|doi=10.2165/00002018-200528020-00001|pmid=15691220|s2cid=11570020}}</ref> Although [[Thiomersal controversy|controversial claims]] have been made that thiomersal contributes to [[autism spectrum disorder|autism]], no convincing scientific evidence supports these claims.<ref>{{cite journal|author-link=Paul Offit|vauthors=Offit PA|date=September 2007|title=Thimerosal and vaccines – a cautionary tale|journal=The New England Journal of Medicine|volume=357|issue=13|pages=1278–1279|doi=10.1056/NEJMp078187|pmid=17898096|s2cid=36318722|doi-access=free}}</ref> Furthermore, a 10–11-year study of 657,461 children found that the [[MMR vaccine and autism|MMR vaccine does not cause autism]] and actually reduced the risk of autism by seven percent.<ref>{{Cite news|date=5 March 2019|title=Another study, this one of 657k kids, finds MMR vaccine doesn't cause autism |newspaper=National Post|url=https://nationalpost.com/news/world/the-largest-ever-study-has-shown-the-measles-mumps-and-rubella-vaccine-is-linked-to-lower-rates-of-autism|access-date=13 March 2019}}</ref><ref>{{Cite news|last=Hoffman|first=Jan|date=5 March 2019|title=One More Time, With Big Data: Measles Vaccine Doesn't Cause Autism|work=The New York Times|url=https://www.nytimes.com/2019/03/05/health/measles-vaccine-autism.html|access-date=13 March 2019|issn=0362-4331|name-list-style=vanc|archive-date=12 March 2019|archive-url=https://web.archive.org/web/20190312175816/https://www.nytimes.com/2019/03/05/health/measles-vaccine-autism.html|url-status=live}}</ref>

===Excipients===
Beside the active vaccine itself, the following [[excipient]]s and residual manufacturing compounds are present or may be present in vaccine preparations:<ref name="cdc">{{cite web|author=CDC|date=12 July 2018|title=Ingredients of Vaccines – Fact Sheet|url=https://www.cdc.gov/vaccines/vac-gen/additives.htm|url-status=live|archive-url=https://web.archive.org/web/20091217193639/http://www.cdc.gov/vaccines/vac-gen/additives.htm|archive-date=17 December 2009|access-date=20 December 2009}}</ref>
* [[Aluminum]] salts or gels are added as [[adjuvant]]s. Adjuvants are added to promote an earlier, more potent response, and more persistent immune response to the vaccine; they allow for a lower vaccine dosage.
* [[Antibiotic]]s are added to some vaccines to prevent the growth of bacteria during production and storage of the vaccine.
* Egg [[protein]] is present in the [[influenza vaccine]] and [[yellow fever vaccine]] as they are prepared using chicken eggs. Other proteins may be present.
* [[Formaldehyde]] is used to inactivate bacterial products for toxoid vaccines. Formaldehyde is also used to inactivate unwanted viruses and kill bacteria that might contaminate the vaccine during production.
* [[Monosodium glutamate]] (MSG) and 2-[[phenoxyethanol]] are used as stabilizers in a few vaccines to help the vaccine remain unchanged when the vaccine is exposed to heat, light, acidity, or humidity.
* [[Thiomersal]] is a mercury-containing antimicrobial that is added to vials of vaccines that contain more than one dose to prevent contamination and growth of potentially harmful bacteria. Due to the controversy surrounding thiomersal, it has been removed from most vaccines except multi-use influenza, where it was reduced to levels so that a single dose contained less than a microgram of mercury, a level similar to eating ten grams of canned tuna.<ref name="FDA">The mercury levels in the table, unless otherwise indicated, are taken from [https://www.fda.gov/Food/FoodborneIllnessContaminants/Metals/ucm115644.htm Mercury Levels in Commercial Fish and Shellfish (1990–2010)] {{webarchive|url=https://web.archive.org/web/20150503155319/https://www.fda.gov/Food/FoodborneIllnessContaminants/metals/ucm115644.htm|date=3 May 2015}} U.S. Food and Drug Administration. Accessed 8{{spaces}}January 2012.</ref>

==Nomenclature==
Various fairly standardized abbreviations for vaccine names have developed, although the standardization is by no means centralized or global. For example, the vaccine names used in the United States have well-established abbreviations that are also widely known and used elsewhere. An extensive list of them provided in a sortable table and freely accessible is available at a US [[Centers for Disease Control and Prevention]] web page.<ref name="CDC_US_vaccine_names">{{Citation |author=Centers for Disease Control and Prevention |title=U.S. Vaccine Names |date=12 November 2020 |url=https://www.cdc.gov/vaccines/terms/usvaccines.html |access-date=21 August 2021 |postscript=. |archive-date=21 August 2021 |archive-url=https://web.archive.org/web/20210821174655/https://www.cdc.gov/vaccines/terms/usvaccines.html |url-status=live }}</ref> The page explains that "The abbreviations [in] this table (Column 3) were standardized jointly by staff of the Centers for Disease Control and Prevention, [[Advisory Committee on Immunization Practices|ACIP]] Work Groups, the editor of the ''[[Morbidity and Mortality Weekly Report]]'' (MMWR), the editor of ''Epidemiology and Prevention of Vaccine-Preventable Diseases'' (the Pink Book), ACIP members, and liaison organizations to the ACIP."<ref name="CDC_US_vaccine_names"/>

Some examples are "[[DTaP]]" for diphtheria and tetanus toxoids and acellular pertussis vaccine, "DT" for diphtheria and tetanus toxoids, and "Td" for tetanus and diphtheria toxoids. At its page on tetanus vaccination,<ref name="CDC_tetanus_vaccination">{{Citation |author=Centers for Disease Control and Prevention |title=Tetanus (Lockjaw) Vaccination |url=https://www.cdc.gov/vaccines/vpd-vac/tetanus/ |access-date=21 May 2016 |postscript=. |url-status=live |archive-url=https://web.archive.org/web/20160516034254/http://www.cdc.gov/vaccines/vpd-vac/tetanus/ |archive-date=16 May 2016 |date=7 August 2018 }}</ref> the CDC further explains that "Upper-case letters in these abbreviations denote full-strength doses of diphtheria (D) and tetanus (T) toxoids and pertussis (P) vaccine. Lower-case "d" and "p" denote reduced doses of diphtheria and pertussis used in the adolescent/adult-formulations. The 'a' in DTaP and Tdap stands for 'acellular', meaning that the pertussis component contains only a part of the pertussis organism."<ref name="CDC_tetanus_vaccination" />

Another list of established vaccine abbreviations is at the CDC's page called "Vaccine Acronyms and Abbreviations", with abbreviations used on U.S. immunization records.<ref name="CDC_US_vaccine_abbreviations">{{Citation |author=Centers for Disease Control and Prevention |title=Vaccine Acronyms and Abbreviations [Abbreviations used on U.S. immunization records] |url=https://www.cdc.gov/vaccines/terms/vacc-abbrev.html |access-date=22 May 2017 |postscript=. |url-status=live |archive-url=https://web.archive.org/web/20170602192710/https://www.cdc.gov/vaccines/terms/vacc-abbrev.html |archive-date=2 June 2017 |date=2 February 2018 }}</ref> The [[United States Adopted Name]] system has some conventions for the [[word order]] of vaccine names, placing [[head (linguistics)|head nouns]] first and [[postpositive adjective|adjectives postpositively]]. This is why the USAN for "[[polio vaccine|OPV]]" is "poliovirus vaccine live oral" rather than "oral poliovirus vaccine".

==Licensing==
{{see also|Vaccine trial}}
A vaccine ''licensure'' occurs after the successful conclusion of the development cycle and further the clinical trials and other programs involved through [[Phases of clinical research|Phases]]{{spaces}}I–III demonstrating safety, immunoactivity, immunogenetic safety at a given specific dose, proven effectiveness in preventing infection for target populations, and enduring preventive effect (time endurance or need for revaccination must be estimated).<ref name="who-vacc">{{cite web|date=1 April 2014|title=Principles and considerations for adding a vaccine to a national immunization programme|url=https://apps.who.int/iris/bitstream/handle/10665/111548/9789241506892_eng.pdf|url-status=live|archive-url=https://web.archive.org/web/20200929164919/https://apps.who.int/iris/bitstream/handle/10665/111548/9789241506892_eng.pdf|archive-date=29 September 2020|access-date=17 August 2020|publisher=[[World Health Organization]] (WHO)}}</ref> Because preventive vaccines are predominantly evaluated in healthy population cohorts and distributed among the general population, a high standard of safety is required.<ref>{{cite journal |last1=Bok |first1=Karin |last2=Sitar |first2=Sandra |last3=Graham |first3=Barney S. |author4-link=John R. Mascola |last4=Mascola |first4=John R. |title=Accelerated COVID-19 vaccine development: milestones, lessons, and prospects |journal=Immunity |date=August 2021 |volume=54 |issue=8 |pages=1636–1651 |doi=10.1016/j.immuni.2021.07.017|pmid=34348117 |pmc=8328682 }}</ref> As part of a multinational licensing of a vaccine, the World Health Organization ''Expert Committee on Biological Standardization'' developed guidelines of international standards for manufacturing and [[quality control]] of vaccines, a process intended as a platform for national regulatory agencies to apply for their own licensing process.<ref name="who-vacc" /> Vaccine manufacturers do not receive licensing until a complete clinical cycle of development and trials proves the vaccine is safe and has long-term effectiveness, following scientific review by a multinational or national regulatory organization, such as the [[European Medicines Agency]] (EMA) or the US [[Food and Drug Administration]] (FDA).<ref name="wijnans">{{cite journal|last1=Wijnans|first1=Leonoor|last2=Voordouw|first2=Bettie|date=11 December 2015|title=A review of the changes to the licensing of influenza vaccines in Europe|journal=Influenza and Other Respiratory Viruses|volume=10|issue=1|pages=2–8|doi=10.1111/irv.12351|issn=1750-2640|pmc=4687503|pmid=26439108}}</ref><ref name="chop">{{cite web|last=Offit|first=Paul A.|year=2020|title=Making vaccines: Licensure, recommendations and requirements|url=https://www.chop.edu/centers-programs/vaccine-education-center/making-vaccines/licensure-recommendations-and-requirements|url-status=live|archive-url=https://web.archive.org/web/20200908060918/https://www.chop.edu/centers-programs/vaccine-education-center/making-vaccines/licensure-recommendations-and-requirements|archive-date=8 September 2020|access-date=20 August 2020|publisher=Children's Hospital of Philadelphia}}</ref>

Upon [[Developing country|developing countries]] adopting WHO guidelines for vaccine development and licensure, each country has its own responsibility to issue a national licensure, and to manage, deploy, and monitor the vaccine throughout its use in each nation.<ref name="who-vacc" /> Building trust and acceptance of a licensed vaccine among the public is a task of communication by governments and healthcare personnel to ensure a vaccination campaign proceeds smoothly, saves lives, and enables economic recovery.<ref name="toner">{{cite report|url=https://www.centerforhealthsecurity.org/our-work/pubs_archive/pubs-pdfs/2020/200819-vaccine-allocation.pdf|title=Interim Framework for COVID-19 Vaccine Allocation and Distribution in the United States|publisher=Johns Hopkins Center for Health Security|access-date=24 August 2020|archive-url=https://web.archive.org/web/20200822093641/https://www.centerforhealthsecurity.org/our-work/pubs_archive/pubs-pdfs/2020/200819-vaccine-allocation.pdf|archive-date=22 August 2020|vauthors=Toner E, Barnill A, Krubiner C, Bernstein J, Privor-Dumm L, Watson M, Martin E, Potter C, Hosangadi D, Connell N, Watson C, Schoch-Spana M, Veenema TG, Meyer D, Biddison EL, Regenberg A, Inglesby T, Cicero A|display-authors=6|publication-place=Baltimore, MD|year=2020|url-status=live}}</ref><ref>{{cite journal|last1=Dooling|first1=Kathleen|last2=Marin|first2=Mona|last3=Wallace|first3=Megan|last4=McClung|first4=Nancy|last5=Chamberland|first5=Mary|last6=Lee|first6=Grace M.|last7=Talbot|first7=H. Keipp|last8=Romero|first8=José R.|last9=Bell|first9=Beth P.|last10=Oliver|first10=Sara E.|display-authors=6|date=December 2020|title=The Advisory Committee on Immunization Practices' Updated Interim Recommendation for Allocation of COVID-19 Vaccine – United States, December 2020|journal=MMWR. Morbidity and Mortality Weekly Report|volume=69|issue=5152|pages=1657–1660|doi=10.15585/mmwr.mm695152e2|pmid=33382671|pmc=9191902 |doi-access=free|name-list-style=vanc}}</ref> When a vaccine is licensed, it will initially be in limited supply due to variable manufacturing, distribution, and logistical factors, requiring an allocation plan for the limited supply and which population segments should be prioritized to first receive the vaccine.<ref name="toner" />

===World Health Organization===
Vaccines developed for multinational distribution via the [[UNICEF|United Nations Children's Fund (UNICEF)]] require pre-qualification by the WHO to ensure [[international standard]]s of quality, safety, immunogenicity, and efficacy for adoption by numerous countries.<ref name="who-vacc" />

The process requires manufacturing consistency at WHO-contracted laboratories following [[Good Manufacturing Practice]] (GMP).<ref name="who-vacc" /> When UN agencies are involved in vaccine licensure, individual nations collaborate by 1) issuing marketing authorization and a national license for the vaccine, its manufacturers, and distribution partners; and 2) conducting [[postmarketing surveillance]], including records for adverse events after the vaccination program. The WHO works with national agencies to monitor inspections of manufacturing facilities and distributors for compliance with GMP and regulatory oversight.<ref name="who-vacc" />

Some countries choose to buy vaccines licensed by reputable national organizations, such as EMA, FDA, or national agencies in other affluent countries, but such purchases typically are more expensive and may not have distribution resources suitable to local conditions in developing countries.<ref name="who-vacc" />

===European Union===
In the European Union (EU), vaccines for pandemic pathogens, such as [[seasonal influenza]], are licensed EU-wide where all the [[Member state of the European Union|member states]] comply ("centralized"), are licensed for only some member states ("decentralized"), or are licensed on an individual national level.<ref name="wijnans" /> Generally, all EU states follow regulatory guidance and clinical programs defined by the European [[Committee for Medicinal Products for Human Use]] (CHMP), a scientific panel of the [[European Medicines Agency]] (EMA) responsible for vaccine licensure.<ref name="wijnans" /> The CHMP is supported by several expert groups who assess and monitor the progress of a vaccine before and after licensure and distribution.<ref name="wijnans" />

===United States===
Under the FDA, the process of establishing evidence for vaccine clinical safety and efficacy is the same as for [[Drug approval|the approval process for prescription drugs]].<ref name="fda-vacc">{{cite web|date=30 January 2020|title=Vaccine product approval process|url=https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/vaccine-product-approval-process|archive-url=https://web.archive.org/web/20200927144627/https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/vaccine-product-approval-process|archive-date=27 September 2020|access-date=17 August 2020|publisher=U.S. [[Food and Drug Administration]] (FDA)}}</ref> If successful through the stages of clinical development, the vaccine licensing process is followed by a [[Biologics License Application]] which must provide a scientific review team (from diverse disciplines, such as physicians, statisticians, microbiologists, chemists) and comprehensive documentation for the vaccine candidate having efficacy and safety throughout its development. Also during this stage, the proposed manufacturing facility is examined by expert reviewers for GMP compliance, and the label must have a compliant description to enable health care providers' definition of vaccine-specific use, including its possible risks, to communicate and deliver the vaccine to the public.<ref name="fda-vacc" /> After licensure, monitoring of the vaccine and its production, including periodic inspections for GMP compliance, continue as long as the manufacturer retains its license, which may include additional submissions to the FDA of tests for potency, safety, and purity for each vaccine manufacturing step.<ref name="fda-vacc" />

===India===
In India, the [[Drugs Controller General of India|Drugs Controller General]], the head of department of the [[Central Drugs Standard Control Organization]], India's national regulatory body for cosmetics, pharmaceuticals and medical devices, is responsible for the approval of licences for specified categories of drugs such as vaccines and other medicinal items, such as blood or blood products, IV fluids, and sera.<ref>{{cite web |url=https://cdsco.gov.in/opencms/opencms/en/Home/ |title=home |publisher=Cdsco.gov.in |date=15 April 2021 |access-date=10 January 2022 |archive-date=4 January 2022 |archive-url=https://web.archive.org/web/20220104201219/https://cdsco.gov.in/opencms/opencms/en/Home/ |url-status=live }}</ref>

===Postmarketing surveillance===
Until a vaccine is in use amongst the general population, all potential [[Vaccine adverse event|adverse events]] from the vaccine may not be known, requiring manufacturers to conduct [[Phase IV trial|Phase{{spaces}}IV]] studies for [[postmarketing surveillance]] of the vaccine while it is used widely in the public.<ref name="who-vacc" /><ref name="fda-vacc" /> The WHO works with UN member states to implement post-licensing surveillance.<ref name="who-vacc" /> The FDA relies on a [[Vaccine Adverse Event Reporting System]] to monitor safety concerns about a vaccine throughout its use in the American public.<ref name="fda-vacc" />

==Scheduling==
{{main|Vaccination schedule}}
{{For|country-specific information on vaccination policies and practices|Vaccination policy}}
[[File:Share of children who receive key vaccines in target populations, OWID.svg|thumb|upright=1.6]]

In order to provide the best protection, children are recommended to receive vaccinations as soon as their immune systems are sufficiently developed to respond to particular vaccines, with additional "booster" shots often required to achieve "full immunity". This has led to the development of complex vaccination schedules. Global recommendations of vaccination schedule are issued by [[Strategic Advisory Group of Experts]] and will be further translated by [[National Immunization Technical Advisory Group|advisory committee]] at the country level with considering of local factors such as disease epidemiology, acceptability of vaccination, equity in local populations, and programmatic and financial constraint.<ref>{{cite journal|title=Evidence-informed vaccination decision-making in countries: Progress, challenges and opportunities|first1=Christoph A.|last1=Steffen|first2=Louise|last2=Henaff|first3=Antoine|last3=Durupt|first4=Nathalie|last4=El Omeiri|first5=Sidy|last5=Ndiaye|first6=Nyambat|last6=Batmunkh|first7=Jayantha B. L.|last7=Liyanage|first8=Quamrul|last8=Hasan|first9=Liudmila|last9=Mosina|first10=Ian|last10=Jones|first11=Katherine|last11=O'Brien|first12=Joachim|last12=Hombach|publisher=Elsevier|journal=Vaccine|volume=39|issue=15|date=8 April 2021|pages=2146–2152|doi=10.1016/j.vaccine.2021.02.055|pmid=33712350|display-authors=2|doi-access=free}}</ref> In the United States, the [[Advisory Committee on Immunization Practices]], which recommends schedule additions for the [[Centers for Disease Control and Prevention]], recommends routine vaccination of children against<ref>{{cite web | url=https://www.cdc.gov/vaccines/hcp/acip-recs/index.html | title=ACIP Vaccine Recommendations Home Page | author=<!--staff--> | publisher=CDC | access-date=10 January 2014 | date=15 November 2013<!--last update--> | url-status=live | archive-url=https://web.archive.org/web/20131231054216/http://www.cdc.gov/vaccines/hcp/acip-recs/index.html | archive-date=31 December 2013 }}</ref> [[hepatitis A]], [[hepatitis B virus|hepatitis B]], polio, mumps, measles, rubella, [[diphtheria]], [[pertussis]], [[tetanus]], [[Haemophilus influenzae|HiB]], chickenpox, [[rotavirus]], [[influenza]], [[meningococcal disease]] and [[pneumonia]].<ref>{{cite web | url=http://aapredbook.aappublications.org/site/news/vaccstatus.xhtml | title=Vaccine Status Table | work=Red Book Online | publisher=American Academy of Pediatrics | date=26 April 2011 | access-date=9 January 2013 | url-status=live | archive-url=https://web.archive.org/web/20131227223436/http://aapredbook.aappublications.org/site/news/vaccstatus.xhtml | archive-date=27 December 2013 }}</ref>

The large number of vaccines and boosters recommended (up to 24 injections by age two) has led to problems with achieving full compliance. To combat declining compliance rates, various notification systems have been instituted and many combination injections are now marketed (e.g., [[Pentavalent vaccine]] and [[MMRV vaccine]]), which protect against multiple diseases.

Besides recommendations for infant vaccinations and boosters, many specific vaccines are recommended for other ages or for repeated injections throughout life{{snd}}most commonly for measles, tetanus, influenza, and pneumonia. Pregnant women are often screened for continued resistance to rubella. The [[human papillomavirus]] vaccine is recommended in the U.S. (as of 2011)<ref>{{cite web | title=HPV Vaccine Safety | url=https://www.cdc.gov/vaccinesafety/Vaccines/HPV/Index.html | publisher=Centers for Disease Control and Prevention (CDC) | date=20 December 2013<!--last update--> | access-date=10 January 2014 | url-status=live | archive-url=https://web.archive.org/web/20091110193757/http://www.cdc.gov/vaccinesafety/Vaccines/HPV/Index.html | archive-date=10 November 2009 }}</ref> and UK (as of 2009).<ref>{{cite news | title=HPV vaccine in the clear | author=<!--staff--> | url=http://www.nhs.uk/news/2009/09September/Pages/Cervical-cancer-vaccine-QA.aspx | work=NHS choices | date=2 October 2009 | access-date=10 January 2014 | url-status=live | archive-url=https://web.archive.org/web/20140110093039/http://www.nhs.uk/news/2009/09September/Pages/Cervical-cancer-vaccine-QA.aspx | archive-date=10 January 2014}}</ref> Vaccine recommendations for the elderly concentrate on pneumonia and influenza, which are more deadly to that group. In 2006, a vaccine was introduced against [[Herpes zoster|shingles]], a disease caused by the chickenpox virus, which usually affects the elderly.<ref name="Zostavax EPAR">{{cite web | title=Zostavax EPAR | website=[[European Medicines Agency]] (EMA) | url=https://www.ema.europa.eu/en/medicines/human/EPAR/zostavax | access-date=1 September 2021 | date=29 July 2021 | archive-date=5 August 2020 | archive-url=https://web.archive.org/web/20200805022553/https://www.ema.europa.eu/en/medicines/human/EPAR/zostavax | url-status=live }}</ref>

Scheduling and dosing of a vaccination may be tailored to the level of immunocompetence of an individual<ref>{{Cite journal|last=Dooling|first=Kathleen|date=13 August 2021|title=The Advisory Committee on Immunization Practices' Updated Interim Recommendation for Allocation of COVID-19 Vaccine – United States, December 2020|url=https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-08-13/02-COVID-Dooling-508.pdf|journal=CDC the Advisory Committee on Immunization Practices.|volume=69|issue=5152|pages=1657–1660|pmid=33382671|pmc=9191902|access-date=17 August 2021|archive-date=19 August 2021|archive-url=https://web.archive.org/web/20210819101406/https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-08-13/02-COVID-Dooling-508.pdf|url-status=live}}</ref> and to optimize population-wide deployment of a vaccine when its supply is limited,<ref>{{Cite journal|last=Hunziker|first=Patrick|date=24 July 2021|title=Personalized-dose Covid-19 vaccination in a wave of virus Variants of Concern: Trading individual efficacy for societal benefit|url=https://precisionnanomedicine.com/article/26101-personalized-dose-covid-19-vaccination-in-a-wave-of-virus-variants-of-concern-trading-individual-efficacy-for-societal-benefit|journal=Precision Nanomedicine|volume=4|issue=3|pages=805–820|doi=10.33218/001c.26101|issn=2639-9431|doi-access=free|access-date=17 August 2021|archive-date=9 October 2021|archive-url=https://web.archive.org/web/20211009194402/https://precisionnanomedicine.com/article/26101-personalized-dose-covid-19-vaccination-in-a-wave-of-virus-variants-of-concern-trading-individual-efficacy-for-societal-benefit|url-status=live}}</ref> e.g. in the setting of a pandemic.

==Economics of development==
{{main|Economics of vaccines}}

One challenge in vaccine development is economic: Many of the diseases most demanding a vaccine, including [[HIV]], [[malaria]] and tuberculosis, exist principally in poor countries. In the United States, financial returns are usually minimal and the financial and other risks are great.<ref name="market_return">{{cite news | first=Jesse L. | last=Goodman | name-list-style = vanc | title=Statement by Jesse L. Goodman, M.D., M.P.H. Director Center for Biologics, Evaluation and Research Food and Drug Administration U.S. Department of Health and Human Services on US Influenza Vaccine Supply and Preparations for the Upcoming Influenza Season before Subcommittee on Oversight and Investigations Committee on Energy and Commerce United States House of Representatives | date=4 May 2005 | url=https://www.hhs.gov/asl/testify/t050504b.html | access-date=15 June 2008 | url-status=dead | archive-url=https://web.archive.org/web/20080921163050/http://www.hhs.gov/asl/testify/t050504b.html | archive-date=21 September 2008 }}</ref>

Most vaccine development to date has relied on "push" funding by government, universities and non-profit organizations.<ref>{{cite journal | vauthors = Olesen OF, Lonnroth A, Mulligan B | title = Human vaccine research in the European Union | journal = Vaccine | volume = 27 | issue = 5 | pages = 640–645 | date = January 2009 | pmid = 19059446 | doi = 10.1016/j.vaccine.2008.11.064 | pmc = 7115654 }}</ref> Many vaccines have been highly cost effective and beneficial for [[public health]].<ref>{{cite journal | vauthors = Jit M, Newall AT, Beutels P | title = Key issues for estimating the impact and cost-effectiveness of seasonal influenza vaccination strategies | journal = Human Vaccines & Immunotherapeutics | volume = 9 | issue = 4 | pages = 834–840 | date = April 2013 | pmid = 23357859 | pmc = 3903903 | doi = 10.4161/hv.23637 }}</ref> The number of vaccines actually administered has risen dramatically in recent decades.<ref>{{cite journal | vauthors = Newall AT, Reyes JF, Wood JG, McIntyre P, Menzies R, Beutels P | title = Economic evaluations of implemented vaccination programmes: key methodological challenges in retrospective analyses | journal = Vaccine | volume = 32 | issue = 7 | pages = 759–765 | date = February 2014 | pmid = 24295806 | doi = 10.1016/j.vaccine.2013.11.067 }}</ref> This increase, particularly in the number of different vaccines administered to children before entry into schools, may be due to government mandates and support, rather than economic incentive.<ref>{{Cite journal|last1=Roser|first1=Max|last2=Vanderslott|first2=Samantha|date=10 May 2013|title=Vaccination|url=https://ourworldindata.org/vaccination|journal=Our World in Data|access-date=3 May 2019|archive-date=1 September 2020|archive-url=https://web.archive.org/web/20200901093537/https://ourworldindata.org/vaccination|url-status=live}}</ref>

===Patents===
According to the [[World Health Organization]] (WHO), the biggest barrier to vaccine production in less developed countries has not been [[patent]]s, but the substantial financial, [[infrastructure]], and workforce requirements needed for market entry. Vaccines are complex mixtures of biological compounds, and unlike the case for [[prescription drug]]s, there are no true [[generic drug|generic vaccines]]. The vaccine produced by a new facility must undergo complete clinical testing for safety and efficacy by the manufacturer. For most vaccines, specific processes in technology are patented. These can be circumvented by alternative manufacturing methods, but this required R&D infrastructure and a suitably skilled workforce. In the case of a few relatively new vaccines, such as the [[human papillomavirus]] vaccine, the patents may impose an additional barrier.<ref>{{cite web|title=Increasing Access to Vaccines Through Technology Transfer and Local Production|publisher=[[World Health Organization]] (WHO)|date=2011|url=https://www.who.int/phi/publications/Increasing_Access_to_Vaccines_Through_Technology_Transfer.pdf|url-status=live|archive-url=https://web.archive.org/web/20151123091841/http://www.who.int/phi/publications/Increasing_Access_to_Vaccines_Through_Technology_Transfer.pdf|archive-date=23 November 2015}}</ref>

When increased production of vaccines was urgently needed during the [[COVID-19 pandemic]] in 2021, the [[World Trade Organization]] and governments around the world evaluated whether to waive [[intellectual property]] rights and patents on [[COVID-19 vaccine]]s, which would "eliminate all potential barriers to the timely access of affordable COVID-19 medical products, including vaccines and medicines, and scale up the manufacturing and supply of essential medical products".<ref name="somos">{{cite news |author1=Christy Somos |title=Everything you need to know about the WTO's COVID-19 vaccine patent proposal |url=https://www.ctvnews.ca/health/coronavirus/everything-you-need-to-know-about-the-wto-s-covid-19-vaccine-patent-proposal-1.5418708 |access-date=23 May 2021 |work=CTV News |date=7 May 2021 |archive-date=23 May 2021 |archive-url=https://web.archive.org/web/20210523145416/https://www.ctvnews.ca/health/coronavirus/everything-you-need-to-know-about-the-wto-s-covid-19-vaccine-patent-proposal-1.5418708 |url-status=dead }}</ref>

==Production==
[[File:Preparation of measles vaccines.jpg|thumb| Preparation of measles vaccine at the Tirana (Albania) Institute of Hygiene and Epidemiology.]]

Vaccine production is fundamentally different from other kinds of manufacturing{{snd}}including regular [[pharmaceutical manufacturing]]{{snd}}in that vaccines are intended to be administered to millions of people of whom the vast majority are perfectly healthy.<ref name="Plotkin_Page_45">{{cite book |last1=Gomez |first1=Phillip L. |last2=Robinson |first2=James M. |last3=Rogalewicz |first3=James |editor1-last=Plotkin |editor1-first=Stanley A. |editor2-last=Orenstein |editor2-first=Walter A. |editor3-last=Offit |editor3-first=Paul A. |title=[[Plotkin's Vaccines|Vaccines]] |date=2008 |publisher=Saunders Elsevier |location=New York |isbn=978-1-4377-2158-4 |pages=45–58 |edition=5th |chapter-url=https://books.google.com/books?id=ncxAHU67EoYC&pg=PT1 |access-date=26 March 2021 |chapter=Chapter 4: Vaccine Manufacturing |archive-date=18 April 2023 |archive-url=https://web.archive.org/web/20230418101022/https://books.google.com/books?id=ncxAHU67EoYC&pg=PT1 |url-status=live }}</ref> This fact drives an extraordinarily rigorous production process with strict compliance requirements that go far beyond what is required of other products.<ref name="Plotkin_Page_45" />

Depending upon the antigen, it can cost anywhere from US$50 to $500 million to build a vaccine production facility, which requires highly specialized equipment, [[Cleanroom|clean rooms]], and containment rooms.<ref name="Plotkin_2017">{{cite journal |last1=Plotkin |first1=Stanley |last2=Robinson |first2=James M. |last3=Cunningham |first3=Gerard |last4=Iqbal |first4=Robyn |last5=Larsen |first5=Shannon |title=The complexity and cost of vaccine manufacturing – An overview |journal=Vaccine |date=24 July 2017 |volume=35 |issue=33 |pages=4064–4071 |doi=10.1016/j.vaccine.2017.06.003 |pmid=28647170 |pmc=5518734 }}</ref> There is a global scarcity of personnel with the right combination of skills, expertise, knowledge, competence and personality to staff vaccine production lines.<ref name="Plotkin_2017" /> With the notable exceptions of Brazil, China, and India, many developing countries' educational systems are unable to provide enough qualified candidates, and vaccine makers based in such countries must hire expatriate personnel to keep production going.<ref name="Plotkin_2017" />

Vaccine production has several stages. First, the antigen itself is generated. Viruses are grown either on primary cells such as [[Chicken as biological research model|chicken eggs]] (e.g., for influenza) or on continuous cell lines such as cultured human cells (e.g., for [[hepatitis A]]).<ref>{{Cite news|url = https://www.washingtonpost.com/wp-dyn/content/graphic/2009/11/24/GR2009112401834.html?sid=ST2009112401941|title = Three ways to make a vaccine|access-date = 5 August 2015|type = infographic|postscript = none|url-status=live|archive-url = https://web.archive.org/web/20151223231412/http://www.washingtonpost.com/wp-dyn/content/graphic/2009/11/24/GR2009112401834.html?sid=ST2009112401941|archive-date = 23 December 2015}}, in {{Cite news|url = https://www.washingtonpost.com/wp-dyn/content/story/2009/11/24/ST2009112401941.html?sid=ST2009112401941|title = Vaccine system remains antiquated|last = Stein|first = Rob|date = 24 November 2009|work = [[Wash. Post|The Washington Post]]|url-status=live|archive-url = https://web.archive.org/web/20171019084922/http://www.washingtonpost.com/wp-dyn/content/story/2009/11/24/ST2009112401941.html?sid=ST2009112401941|archive-date = 19 October 2017}}</ref> Bacteria are grown in [[bioreactor]]s (e.g., ''[[Haemophilus influenzae]]'' type b). Likewise, a recombinant protein derived from the viruses or bacteria can be generated in yeast, bacteria, or cell cultures.<ref name=":0" /><ref name="WHOVaccSafety2" />

After the antigen is generated, it is isolated from the cells used to generate it. A virus may need to be inactivated, possibly with no further purification required. Recombinant proteins need many operations involving ultrafiltration and column chromatography. Finally, the vaccine is formulated by adding adjuvant, stabilizers, and preservatives as needed. The adjuvant enhances the immune response to the antigen, stabilizers increase the storage life, and preservatives allow the use of multidose vials.<ref name=":0">{{cite journal | vauthors = Muzumdar JM, Cline RR | title = Vaccine supply, demand, and policy: a primer | journal = Journal of the American Pharmacists Association | volume = 49 | issue = 4 | pages = e87–99 | year = 2009 | pmid = 19589753 | doi = 10.1331/JAPhA.2009.09007 | pmc = 7185851 }}</ref><ref name="WHOVaccSafety2">{{cite web |url=http://vaccine-safety-training.org/vaccine-components.html |title=Components of a vaccine |url-status=live |archive-url=https://web.archive.org/web/20170613192256/http://vaccine-safety-training.org/vaccine-components.html |archive-date=13 June 2017 }}</ref> Combination vaccines are harder to develop and produce, because of potential incompatibilities and interactions among the antigens and other ingredients involved.<ref name="Bae" />

The final stage in vaccine manufacture before distribution is [[fill and finish]], which is the process of filling vials with vaccines and packaging them for distribution. Although this is a conceptually simple part of the vaccine manufacture process, it is often a bottleneck in the process of distributing and administering vaccines.<ref>{{cite web|date=6 April 2020|title=Vaccine Taskforce Aims|url=https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/893417/S0135_Vaccine_Taskforce_Aims.pdf|access-date=26 July 2020|website=assets.publishing.service.gov.uk|archive-date=26 July 2020|archive-url=https://web.archive.org/web/20200726102641/https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/893417/S0135_Vaccine_Taskforce_Aims.pdf|url-status=live}}</ref><ref>{{Cite journal|last1=Pagliusi|first1=Sonia|last2=Jarrett|first2=Stephen|last3=Hayman|first3=Benoit|last4=Kreysa|first4=Ulrike|last5=Prasad|first5=Sai D.|last6=Reers|first6=Martin|last7=Hong Thai|first7=Pham|last8=Wu|first8=Ke|last9=Zhang|first9=Youn Tao|last10=Baek|first10=Yeong Ok|last11=Kumar|first11=Anand|date=July 2020|title=Emerging manufacturers engagements in the COVID −19 vaccine research, development and supply|journal=Vaccine|volume=38|issue=34|pages=5418–5423|doi=10.1016/j.vaccine.2020.06.022|pmc=7287474|pmid=32600908}}</ref><ref>{{cite web|last1=Miller|first1=Joe|last2=Kuchler|first2=Hannah|date=28 April 2020|title=Drugmakers race to scale up vaccine capacity|url=https://www.ft.com/content/87d1170a-78bc-11ea-bd25-7fd923850377 |archive-url=https://ghostarchive.org/archive/20221210/https://www.ft.com/content/87d1170a-78bc-11ea-bd25-7fd923850377 |archive-date=10 December 2022 |url-access=subscription|access-date=26 July 2020|website=www.ft.com}}</ref>

Vaccine production techniques are evolving. Cultured [[mammalian cells]] are expected to become increasingly important, compared to conventional options such as chicken eggs, due to greater productivity and low incidence of problems with contamination. Recombination technology that produces genetically detoxified vaccines is expected to grow in popularity for the production of bacterial vaccines that use toxoids. Combination vaccines are expected to reduce the quantities of antigens they contain, and thereby decrease undesirable interactions, by using [[pathogen-associated molecular pattern]]s.<ref name=Bae>{{cite journal | vauthors = Bae K, Choi J, Jang Y, Ahn S, Hur B | title = Innovative vaccine production technologies: the evolution and value of vaccine production technologies | journal = Archives of Pharmacal Research | volume = 32 | issue = 4 | pages = 465–480 | date = April 2009 | pmid = 19407962 | doi = 10.1007/s12272-009-1400-1 | s2cid = 9066150 | doi-access = free }}</ref>

===Vaccine manufacturers===
The companies with the highest market share in vaccine production are [[Merck & Co.|Merck]], [[Sanofi]], [[GlaxoSmithKline]], [[Pfizer]] and [[Novartis]], with 70% of vaccine sales concentrated in the EU or US (2013).<ref name=plotkin2017>{{Cite book|title= Vaccines|first1= Stanley A. | last1=Plotkin| first2=Walter A. |last2 =Orenstein| first3= Paul A. |last3=Offit |first4=Kathryn M. |last4=Edwards |publisher=Elsevier |year=2017|isbn=978-0-323-39301-0}}</ref>{{rp|42}} Vaccine manufacturing plants require large capital investments ($50 million up to $300 million) and may take between 4 and 6 years to construct, with the full process of vaccine development taking between 10 and 15 years.<ref name=plotkin2017/>{{rp|43}} Manufacturing in developing countries is playing an increasing role in supplying these countries, specifically with regards to older vaccines and in Brazil, India and China.<ref name=plotkin2017/>{{rp|47}} The manufacturers in India are the most advanced in the developing world and include the [[Serum Institute of India]], one of the largest producers of vaccines by number of doses and an innovator in processes, recently improving efficiency of producing the measles vaccine by 10 to 20-fold, due to switching to a [[MRC-5]] cell culture instead of chicken eggs.<ref name=plotkin2017/>{{rp|48}} China's manufacturing capabilities are focused on supplying their own domestic need, with [[Sinopharm|Sinopharm (CNPGC)]] alone providing over 85% of the doses for 14 different vaccines in China.<ref name=plotkin2017/>{{rp|48}} Brazil is approaching the point of supplying its own domestic needs using technology transferred from the developed world.<ref name=plotkin2017/>{{rp|49}}

==Delivery systems==
[[File:VaccineBySandraRugio.jpg|thumb|right|A woman receiving a vaccine by injection]]

One of the most common methods of delivering vaccines into the human body is [[Injection (medicine)|injection]].

The development of new delivery systems raises the hope of vaccines that are safer and more efficient to deliver and administer. Lines of research include [[liposome]]s and ''[[ISCOM]]'' (immune stimulating complex).<ref>{{cite journal | vauthors = Morein B, Hu KF, Abusugra I | title = Current status and potential application of ISCOMs in veterinary medicine | journal = Advanced Drug Delivery Reviews | volume = 56 | issue = 10 | pages = 1367–1382 | date = June 2004 | pmid = 15191787 | doi = 10.1016/j.addr.2004.02.004 }}</ref>

=== Oral vaccines ===
Notable developments in vaccine delivery technologies have included oral vaccines. Early attempts to apply oral vaccines showed varying degrees of promise, beginning early in the 20th century, at a time when the very possibility of an effective oral antibacterial vaccine was controversial.<ref>{{cite book|title=American Medicine|url=https://books.google.com/books?id=yvxXAAAAMAAJ|year=1926|publisher=American-Medicine Publishing Company}}</ref> By the 1930s there was increasing interest in the prophylactic value of an oral [[typhoid fever]] vaccine for example.<ref name="Research1929">{{cite book|author=South African Institute for Medical Research|title=Annual report [Jaarverslag] |url=https://books.google.com/books?id=KzAXAAAAIAAJ|year=1929|publisher=South African Institute for Medical Research – Suid-Afrikaanse Instituut vir Mediese Navorsing}}</ref>

An [[Polio vaccine|oral polio vaccine]] turned out to be effective when vaccinations were administered by volunteer staff without formal training; the results also demonstrated increased ease and efficiency of administering the vaccines. Effective oral vaccines have many advantages; for example, there is no risk of blood contamination. Vaccines intended for oral administration need not be liquid, and as solids, they commonly are more stable and less prone to damage or spoilage by freezing in transport and storage.<ref>{{cite book|title =Biotechnology Fundamentals | first = Firdos Alam | last = Khan | name-list-style = vanc | publisher=CRC Press| url=https://books.google.com/books?id=-s5oRDUuMSIC&pg=PA270 |page =270|isbn= 978-1-4398-2009-4|year= 2011}}</ref> Such stability reduces the need for a "[[cold chain]]": the resources required to keep vaccines within a restricted temperature range from the manufacturing stage to the point of administration, which, in turn, may decrease costs of vaccines.

=== Microneedle vaccines ===
A microneedle approach, which is still in stages of development, uses "pointed projections fabricated into arrays that can create vaccine delivery pathways through the skin".<ref>{{cite journal | vauthors = Giudice EL, Campbell JD | title = Needle-free vaccine delivery | journal = Advanced Drug Delivery Reviews | volume = 58 | issue = 1 | pages = 68–89 | date = April 2006 | pmid = 16564111 | doi = 10.1016/j.addr.2005.12.003 }}</ref>

=== Dermal patch vaccines ===
An experimental needle-free<ref>[[World Health Organization|WHO]] to trial Nanopatch needle-free delivery system| [[ABC News (Australia)|ABC News]], 16 September 2014| {{cite news |url=http://www.abc.net.au/news/2014-09-16/vaxxas-says-needle-free-polio-vaccine-a-game-changer/5748072 |title=Needle-free polio vaccine a 'game-changer' |newspaper=ABC News |access-date=15 September 2015 |url-status=live |archive-url=https://web.archive.org/web/20150402210010/http://www.abc.net.au/news/2014-09-16/vaxxas-says-needle-free-polio-vaccine-a-game-changer/5748072 |archive-date=2 April 2015 |date=16 September 2014 }}</ref> vaccine delivery system is undergoing animal testing.<ref>{{cite news|title=Australian scientists develop 'needle-free' vaccination|url=http://www.smh.com.au/technology/sci-tech/needleless-trial-set-for-start-20130417-2i0qw.html|newspaper=[[The Sydney Morning Herald]]|date=18 August 2013|url-status=live|archive-url=https://web.archive.org/web/20150925012246/http://www.smh.com.au/technology/sci-tech/needleless-trial-set-for-start-20130417-2i0qw.html|archive-date=25 September 2015}}</ref><ref>{{cite web |url=http://www.brw.com.au/p/tech-gadgets/brisbane_nanopatch_the_reverse_brain_DPyEGHC1ih6919r8X37SdO |website=Business Review Weekly |title=Vaxxas raises $25m to take Brisbane's Nanopatch global |access-date=5 March 2015 |archive-url=https://web.archive.org/web/20150316002836/http://www.brw.com.au/p/tech-gadgets/brisbane_nanopatch_the_reverse_brain_DPyEGHC1ih6919r8X37SdO |archive-date=16 March 2015 |date=10 February 2015 }}</ref> A stamp-size patch similar to an [[adhesive bandage]] contains about 20,000 microscopic projections per square cm.<ref>{{cite news|title=Australian scientists develop 'needle-free' vaccination|url=http://www.thehindu.com/sci-tech/health/medicine-and-research/australian-scientists-develop-needlefree-vaccination/article2493365.ece|newspaper=[[The Hindu]]|date=28 September 2011|location=Chennai, India|url-status=live|archive-url=https://web.archive.org/web/20140101162738/http://www.thehindu.com/sci-tech/health/medicine-and-research/australian-scientists-develop-needlefree-vaccination/article2493365.ece|archive-date=1 January 2014}}</ref> This [[Dermis|dermal]] administration potentially increases the effectiveness of vaccination, while requiring less vaccine than injection.<ref>{{cite web|title=Needle-free nanopatch vaccine delivery system|url=http://www.news-medical.net/news/20110803/Needle-free-nanopatch-vaccine-delivery-system.aspx|publisher=News Medical|date=3 August 2011|url-status=live|archive-url=https://web.archive.org/web/20120511203129/http://www.news-medical.net/news/20110803/Needle-free-nanopatch-vaccine-delivery-system.aspx|archive-date=11 May 2012}}</ref>

==In veterinary medicine==
{{see also|Influenza vaccine#Veterinary use|Vaccination of dogs}}
[[File:US Navy 060815-N-0411D-018 U.S. Army Veterinarian, Capt Gwynne Kinley of Cape Elizabeth, Maine, immunizes a goat with the help of U.S. Navy Operations Specialist 2nd Class Jessica Silva.jpg|thumb|200px|Goat vaccination against [[sheep pox]] and [[pleural pneumonia]]]]

Vaccinations of animals are used both to prevent their contracting diseases and to prevent transmission of disease to humans.<ref>{{cite journal | vauthors = Patel JR, Heldens JG | title = Immunoprophylaxis against important virus disease of horses, farm animals and birds | journal = Vaccine | volume = 27 | issue = 12 | pages = 1797–1810 | date = March 2009 | pmid = 19402200 | doi = 10.1016/j.vaccine.2008.12.063 | pmc = 7130586 }}</ref> Both animals kept as pets and animals raised as livestock are routinely vaccinated. In some instances, wild populations may be vaccinated. This is sometimes accomplished with vaccine-laced food spread in a disease-prone area and has been used to attempt to control [[rabies]] in [[raccoon]]s.

Where rabies occurs, rabies vaccination of dogs may be required by law. Other canine vaccines include [[canine distemper]], [[canine parvovirus]], [[infectious canine hepatitis]], [[Adenoviridae#Animals|adenovirus-2]], [[leptospirosis]], ''[[Bordetella]]'', canine [[parainfluenza virus]], and [[Lyme disease]], among others.

Cases of veterinary vaccines used in humans have been documented, whether intentional or accidental, with some cases of resultant illness, most notably with [[brucellosis]].<ref name="oxford">{{cite journal | vauthors = Berkelman RL | title = Human illness associated with use of veterinary vaccines | journal = Clinical Infectious Diseases | volume = 37 | issue = 3 | pages = 407–414 | date = August 2003 | pmid = 12884166 | doi = 10.1086/375595 | doi-access = free }}</ref> However, the reporting of such cases is rare and very little has been studied about the safety and results of such practices. With the advent of aerosol vaccination in veterinary clinics, human exposure to pathogens not naturally carried in humans, such as ''[[Bordetella bronchiseptica]]'', has likely increased in recent years.<ref name="oxford"/> In some cases, most notably [[Rabies vaccine|rabies]], the parallel veterinary vaccine against a pathogen may be as much as [[orders of magnitude]] more economical than the human one.

===DIVA vaccines===
DIVA (Differentiation of Infected from Vaccinated Animals), also known as SIVA (Segregation of Infected from Vaccinated Animals) vaccines, make it possible to differentiate between infected and vaccinated animals. DIVA vaccines carry at least one [[epitope]] less than the equivalent wild microorganism. An accompanying diagnostic test that detects the antibody against that epitope assists in identifying whether the animal has been vaccinated or not.{{citation needed|date=February 2021}}

The first DIVA vaccines (formerly termed [[marker vaccine]]s and since 1999 coined as DIVA vaccines) and companion diagnostic tests were developed by J. T. van Oirschot and colleagues at the Central Veterinary Institute in Lelystad, The Netherlands.<ref>{{cite journal | vauthors = van Oirschot JT, Rziha HJ, Moonen PJ, Pol JM, van Zaane D | title = Differentiation of serum antibodies from pigs vaccinated or infected with Aujeszky's disease virus by a competitive enzyme immunoassay | journal = The Journal of General Virology | volume = 67 (Pt 6) | issue = 6 | pages = 1179–1182 | date = June 1986 | pmid = 3011974 | doi = 10.1099/0022-1317-67-6-1179 | doi-access = free }}</ref><ref name="ReferenceA">{{cite journal | vauthors = van Oirschot JT | title = Diva vaccines that reduce virus transmission | journal = Journal of Biotechnology | volume = 73 | issue = 2–3 | pages = 195–205 | date = August 1999 | pmid = 10486928 | doi = 10.1016/S0168-1656(99)00121-2 }}</ref> They found that some existing vaccines against [[pseudorabies]] (also termed Aujeszky's disease) had deletions in their viral genome (among which was the gE gene). Monoclonal antibodies were produced against that deletion and selected to develop an [[ELISA]] that demonstrated antibodies against gE. In addition, novel genetically engineered gE-negative vaccines were constructed.<ref>{{cite journal | vauthors = van Oirschot JT, Gielkens AL, Moormann RJ, Berns AJ | title = Marker vaccines, virus protein-specific antibody assays and the control of Aujeszky's disease | journal = Veterinary Microbiology | volume = 23 | issue = 1–4 | pages = 85–101 | date = June 1990 | pmid = 2169682 | doi = 10.1016/0378-1135(90)90139-M }}</ref> Along the same lines, DIVA vaccines and companion diagnostic tests against bovine herpesvirus{{spaces}}1 infections have been developed.<ref name="ReferenceA"/><ref>{{cite journal | vauthors = Kaashoek MJ, Moerman A, Madić J, Rijsewijk FA, Quak J, Gielkens AL, van Oirschot JT | title = A conventionally attenuated glycoprotein E-negative strain of bovine herpesvirus type 1 is an efficacious and safe vaccine | journal = Vaccine | volume = 12 | issue = 5 | pages = 439–444 | date = April 1994 | pmid = 8023552 | doi = 10.1016/0264-410X(94)90122-8 }}</ref>

The DIVA strategy has been applied in various countries to successfully eradicate pseudorabies virus from those countries. Swine populations were intensively vaccinated and monitored by the companion diagnostic test and, subsequently, the infected pigs were removed from the population. Bovine herpesvirus{{spaces}}1 DIVA vaccines are also widely used in practice.{{citation needed|date=February 2021}} Considerable efforts are ongoing to apply the DIVA principle to a wide range of infectious diseases, such as classical swine fever,<ref>{{cite journal | vauthors = Hulst MM, Westra DF, Wensvoort G, Moormann RJ | title = Glycoprotein E1 of hog cholera virus expressed in insect cells protects swine from hog cholera | journal = Journal of Virology | volume = 67 | issue = 9 | pages = 5435–5442 | date = September 1993 | pmid = 8350404 | pmc = 237945 | doi = 10.1128/JVI.67.9.5435-5442.1993 }}</ref> avian influenza,<ref name="pmid12745380">{{cite journal | vauthors = Capua I, Terregino C, Cattoli G, Mutinelli F, Rodriguez JF | title = Development of a DIVA (Differentiating Infected from Vaccinated Animals) strategy using a vaccine containing a heterologous neuraminidase for the control of avian influenza | journal = Avian Pathology | volume = 32 | issue = 1 | pages = 47–55 | date = February 2003 | pmid = 12745380 | doi = 10.1080/0307945021000070714 | s2cid = 22827454 | doi-access = free }}</ref> ''Actinobacillus pleuropneumonia''<ref>{{cite journal | vauthors = Maas A, Meens J, Baltes N, Hennig-Pauka I, Gerlach GF | title = Development of a DIVA subunit vaccine against Actinobacillus pleuropneumoniae infection | journal = Vaccine | volume = 24 | issue = 49–50 | pages = 7226–7237 | date = November 2006 | pmid = 17027123 | doi = 10.1016/j.vaccine.2006.06.047 }}</ref> and ''Salmonella'' infections in pigs.<ref>{{cite journal | vauthors = Leyman B, Boyen F, Van Parys A, Verbrugghe E, Haesebrouck F, Pasmans F | title = Salmonella Typhimurium LPS mutations for use in vaccines allowing differentiation of infected and vaccinated pigs | journal = Vaccine | volume = 29 | issue = 20 | pages = 3679–3685 | date = May 2011 | pmid = 21419163 | doi = 10.1016/j.vaccine.2011.03.004 | url = https://biblio.ugent.be/publication/1201519 | archive-url = https://web.archive.org/web/20171028043359/https://biblio.ugent.be/publication/1201519 | url-status=live | archive-date = 28 October 2017 | hdl = 1854/LU-1201519 | hdl-access = free }}</ref>

==History==
{{Further|Vaccination#History|Inoculation#Origins}}
[[File:Inoculation day 16.png|thumb|Comparison of [[smallpox]] (left) and [[cowpox]] inoculations sixteen days after administration (1802)]]

Prior to the introduction of vaccination with material from cases of cowpox (heterotypic immunisation), smallpox could be prevented by deliberate [[variolation]] with smallpox virus. According to historian [[Joseph Needham]], [[Taoism|Taoists]] in China as far back as the 10th century practiced a form of inoculation and passed it down through oral tradition, though Needham's claim has been criticized since the practice was not written about.<ref name="needham volume 6 part 6 154">{{cite book|last=Needham|first=Joseph |title=Science and Civilisation in China: Volume 6, Biology and Biological Technology, Part 6, Medicine|publisher=Cambridge University Press|year=2000|isbn=978-0-521-63262-1|page=154}}</ref><ref>{{cite journal|author=Boylston A|date=July 2012|title=The origins of inoculation|journal=J R Soc Med|volume=105|issue=7|pages=309–313|doi=10.1258/jrsm.2012.12k044|pmc=3407399|pmid=22843649}}</ref> The Chinese also practiced the oldest documented use of variolation, dating back to the fifteenth century. They implemented a method of "nasal [[Insufflation (medicine)|insufflation]]" administered by blowing powdered smallpox material, usually scabs, up the nostrils. Various insufflation techniques have been recorded throughout the sixteenth and seventeenth centuries within China.<ref name="Williams2010">{{cite book|last=Williams|first=Gareth|title=Angel of Death|publisher=Palgrave Macmillan|year=2010|isbn=978-0-230-27471-6|location=Basingstoke|name-list-style=vanc}}</ref>{{rp|60}} Two reports on the Chinese practice of [[inoculation]] were received by the [[Royal Society]] in London in 1700; one by [[Martin Lister]] who received a report by an employee of the [[East India Company]] stationed in China and another by [[Clopton Havers]].<ref>{{cite book|last=Silverstein|first=Arthur M.|title=A History of Immunology|publisher=Academic Press|year=2009|isbn=978-0-08-091946-1|edition=2nd|page=293}}</ref> In France, [[Voltaire]] reports that the Chinese have practiced variolation "these hundred years".<ref>{{cite book|author=Voltaire|year=1742|title=Letters on the English|chapter=Letter XI|chapter-url=http://www.bartleby.com/34/2/11.html|access-date=26 July 2023|archive-date=16 October 2018|archive-url=https://web.archive.org/web/20181016221306/https://www.bartleby.com/34/2/11.html|url-status=live}}</ref>
[[File:Jenner and his two colleagues seeing off three anti-vaccinat Wellcome V0011075.jpg|thumb|left|An early 19th-century satire of antivaxxers by [[Isaac Cruikshank]]]]

[[Mary Wortley Montagu]], who had witnessed variolation in Turkey, had her four-year-old daughter variolated in the presence of [[physician]]s of the Royal Court in 1721 upon her return to England.<ref name="Williams2010" /> Later on that year, [[Charles Maitland (physician)|Charles Maitland]] conducted an experimental variolation of six prisoners in [[Newgate Prison]] in London.<ref name=fenner1988>{{cite book|title=Smallpox and its Eradication|year=1988|publisher=[[World Health Organization]] (WHO)|location=Geneva|isbn=92-4-156110-6|author=Fenner, F.|author2=Henderson, D.A. |author3=Arita, I. |author4=Jezek, Z. |author5=Ladnyi, I.D. }}</ref> The experiment was a success, and soon variolation was drawing attention from the royal family, who helped promote the procedure. However, in 1783, several days after [[Prince Octavius of Great Britain]] was inoculated, he died.<ref name="Baxby 1984 303–07">{{cite journal|last=Baxby|first=Derrick|title=A Death from Inoculated Smallpox in the English Royal Family|journal=Med Hist|year=1984|volume=28|issue=3|pages=303–307|doi=10.1017/s0025727300035961|pmid=6390027|pmc=1139449}}</ref> 

In 1796, the physician [[Edward Jenner]] took pus from the hand of a milkmaid with [[cowpox]], scratched it into the arm of an 8-year-old boy, [[James Phipps]], and six weeks later variolated the boy with smallpox, afterwards observing that he did not catch smallpox.<ref name="Stern-Markel">{{cite journal|vauthors=Stern AM, Markel H|year=2005|title=The history of vaccines and immunization: familiar patterns, unew challenges|journal=Health Affairs|volume=24|issue=3|pages=611–621|doi=10.1377/hlthaff.24.3.611|pmid=15886151|doi-access=free}}</ref><ref name="Dunn">{{cite journal|vauthors=Dunn PM|date=January 1996|title=Dr Edward Jenner (1749–1823) of Berkeley, and vaccination against smallpox|url=http://fn.bmjjournals.com/content/74/1/F77.full.pdf|journal=Archives of Disease in Childhood: Fetal and Neonatal Edition|volume=74|issue=1|pages=F77–78|doi=10.1136/fn.74.1.F77|pmc=2528332|pmid=8653442|archive-url=https://web.archive.org/web/20110708080506/http://fn.bmjjournals.com/content/74/1/F77.full.pdf|archive-date=8 July 2011}}</ref> Jenner extended his studies and, in 1798, reported that his vaccine was safe in children and adults, and could be transferred from arm-to-arm, which reduced reliance on uncertain supplies from infected cows.<ref name="Baxby 1984 303–07"/> In 1804, the Spanish [[Balmis Expedition|Balmis smallpox vaccination expedition]] to Spain's colonies Mexico and Philippines used the arm-to-arm transport method to get around the fact the vaccine survived for only 12 days ''[[in vitro]]''. They used cowpox.<ref>[https://www.theguardian.com/world/2021/jul/27/spanish-museum-celebrates-pioneer-who-took-smallpox-vaccine-to-colonies Exhibition tells story of Spanish children used as vaccine fridges in 1803] {{Webarchive|url=https://web.archive.org/web/20220830024947/https://www.theguardian.com/world/2021/jul/27/spanish-museum-celebrates-pioneer-who-took-smallpox-vaccine-to-colonies |date=30 August 2022 }} The Guardian, 2021</ref> Since vaccination with cowpox was much safer than smallpox inoculation,<ref>{{cite journal|vauthors=Van Sant JE|year=2008|title=The Vaccinators: Smallpox, Medical Knowledge, and the 'Opening' of Japan|journal=J Hist Med Allied Sci|volume=63|issue=2|pages=276–279|doi=10.1093/jhmas/jrn014}}</ref> the latter, though still widely practiced in England, was banned in 1840.<ref>{{cite journal|vauthors=Didgeon JA|date=May 1963|title=Development of Smallpox Vaccine in England in the Eighteenth and Nineteenth Centuries|journal=British Medical Journal|volume=1|issue=5342|pages=1367–1372|doi=10.1136/bmj.1.5342.1367|pmc=2124036|pmid=20789814}}</ref>
[[File:Centenaire de la découverte de la vaccine par Jenner CIPB0429.jpg|thumb|right|French print in 1896 marking the centenary of Jenner's vaccine]]

Following on from Jenner's work, the second generation of vaccines was introduced in the 1880s by [[Louis Pasteur]] who developed vaccines for [[chicken cholera]] and [[anthrax]],<ref name="Pasteur1881" /> and from the late nineteenth century vaccines were considered a matter of national prestige. National [[vaccination policies]] were adopted and compulsory vaccination laws were passed.<ref name="Stern-Markel" /> In 1931 [[Alice Miles Woodruff]] and [[Ernest Goodpasture]] documented that the [[fowlpox]] virus could be grown in [[embryonated]] chicken [[egg]]. Soon scientists began cultivating other viruses in eggs. Eggs were used for virus propagation in the development of a [[yellow fever vaccine]] in 1935 and an [[influenza vaccine]] in 1945. In 1959 [[growth media]] and [[cell culture]] replaced eggs as the standard method of virus propagation for vaccines.<ref>{{Cite book|title=Essential Human Virology |last1=Louten |first1=Jennifer |publisher=Academic Press|year=2016|isbn=978-0-12-801171-3|pages=134–135}}</ref>

Vaccinology flourished in the twentieth century, which saw the introduction of several successful vaccines, including those against [[diphtheria]], [[measles]], [[mumps]], and [[rubella]]. Major achievements included the development of the [[polio vaccine]] in the 1950s and the [[eradication of smallpox]] during the 1960s and 1970s. [[Maurice Hilleman]] was the most prolific of the developers of the vaccines in the twentieth century. As vaccines became more common, many people began taking them for granted. However, vaccines remain elusive for many important diseases, including [[herpes|herpes simplex]], [[malaria]], [[gonorrhea]], and [[HIV]].<ref name="Stern-Markel" /><ref name="BaardaSikora2015">{{cite journal|vauthors=Baarda BI, Sikora AE|year=2015|title=Proteomics of Neisseria gonorrhoeae: the treasure hunt for countermeasures against an old disease|journal=Frontiers in Microbiology|volume=6|page=1190|doi=10.3389/fmicb.2015.01190|pmc=4620152|pmid=26579097|postscript=;|doi-access=free}}</ref>

===Generations of vaccines===
[[File:Smallpox and anthrax vaccines of 447th Expeditionary Medical Squadron.jpg|thumb|Vials of smallpox and anthrax serum]]

First generation vaccines are whole-organism vaccines{{snd}}either live and [[Attenuated virus|weakened]], or killed forms.<ref name="Alarcon1999">{{cite book|title=Advances in Parasitology Volume 42|vauthors=Alarcon JB, Waine GW, McManus DP|year=1999|isbn=978-0-12-031742-4|volume=42|pages=343–410|chapter=DNA Vaccines: Technology and Application as Anti-parasite and Anti-microbial Agents|doi=10.1016/S0065-308X(08)60152-9|pmid=10050276}}</ref> Live, attenuated vaccines, such as smallpox and polio vaccines, are able to induce [[Cytotoxic T cell|killer T-cell]] (T<sub>C</sub> or CTL) responses, [[Helper T cell|helper T-cell]] (T<sub>H</sub>) responses and antibody [[Immune system|immunity]]. However, attenuated forms of a [[pathogen]] can convert to a dangerous form and may cause disease in [[immunocompromised]] vaccine recipients (such as those with [[AIDS]]). While killed vaccines do not have this risk, they cannot generate specific killer T-cell responses and may not work at all for some diseases.<ref name="Alarcon1999" />

Second generation vaccines were developed to reduce the risks from live vaccines. These are subunit vaccines, consisting of specific [[protein]] antigens (such as [[tetanus]] or [[diphtheria]] [[toxoid]]) or [[Recombinant DNA|recombinant]] protein components (such as the hepatitis B surface [[antigen]]). They can generate T<sub>H</sub> and [[antibody]] responses, but not killer T cell responses.{{citation needed|date=January 2021}}

[[RNA vaccine]]s and [[DNA vaccine]]s are examples of third generation vaccines.<ref name="Alarcon1999" /><ref name="Robinson2000">{{cite book|title=DNA vaccines for viral infections: basic studies and applications|vauthors=Robinson HL, Pertmer TM|year=2000|isbn=978-0-12-039855-3|series=Advances in Virus Research|volume=55|pages=1–74|doi=10.1016/S0065-3527(00)55001-5|pmid=11050940}}</ref><ref>{{cite web |last1=Naftalis |first1=Kramer Levin |last2=Royzman |first2=Frankel LLP-Irena |last3=Pineda |first3=ré |title=Third-Generation Vaccines Take Center Stage in Battle Against COVID-19 {{!}} Lexology |url=https://www.lexology.com/library/detail.aspx?g=04bdfa93-c8ea-4654-a5f1-c659fc4769c8 |website=www.lexology.com |date=30 November 2020 |access-date=24 January 2021 |archive-date=30 January 2021 |archive-url=https://web.archive.org/web/20210130052624/https://www.lexology.com/library/detail.aspx?g=04bdfa93-c8ea-4654-a5f1-c659fc4769c8 |url-status=live }}</ref> In 2016 a DNA vaccine for the [[Zika virus]] began testing at the [[National Institutes of Health]]. Separately, Inovio Pharmaceuticals and GeneOne Life Science began tests of a different DNA vaccine against Zika in Miami. Manufacturing the vaccines in volume was unsolved as of 2016.<ref>{{cite web|last=Regalado|first=Antonio|title=The U.S. government has begun testing its first Zika vaccine in humans|url=https://www.technologyreview.com/s/602073/us-government-starts-test-of-zika-vaccine-in-humans/?set=602081|access-date=6 August 2016|archive-date=21 August 2016|archive-url=https://web.archive.org/web/20160821082930/https://www.technologyreview.com/s/602073/us-government-starts-test-of-zika-vaccine-in-humans/?set=602081|url-status=live}}</ref> Clinical trials for DNA vaccines to prevent HIV are underway.<ref>{{cite journal|vauthors=Chen Y, Wang S, Lu S|date=February 2014|title=DNA Immunization for HIV Vaccine Development|journal=Vaccines|volume=2|issue=1|pages=138–159|doi=10.3390/vaccines2010138|pmc=4494200|pmid=26344472|doi-access=free}}</ref> [[mRNA vaccines]] such as [[BNT162b2]] were developed in the year 2020 with the help of [[Operation Warp Speed]] and massively deployed to combat the [[COVID-19 pandemic]]. In 2021, [[Katalin Karikó]] and [[Drew Weissman]] received Columbia University's Horwitz Prize for their pioneering research in mRNA vaccine technology.<ref>{{cite web|date=12 August 2021|title=Katalin Karikó and Drew Weissman Awarded Horwitz Prize for Pioneering Research on COVID-19 Vaccines|url=https://www.cuimc.columbia.edu/news/horwitz-prize-2021|access-date=7 September 2021|website=Columbia University Irving Medical Center|archive-date=16 August 2021|archive-url=https://web.archive.org/web/20210816131824/https://www.cuimc.columbia.edu/news/horwitz-prize-2021|url-status=live}}</ref>

==Trends==
{{Update section|date=June 2018}}

Since at least 2013, scientists have been trying to develop synthetic third-generation vaccines by reconstructing the outside structure of a [[virus]]; it was hoped that this will help prevent [[vaccine resistance]].<ref>{{Cite news|url = http://www.japantimes.co.jp/news/2013/03/28/world/safer-vaccine-created-without-virus/|title = Safer vaccine created without virus|last = Staff|date = 28 March 2013|work = [[Jpn. Times|The Japan Times]]|access-date = 28 March 2013|agency = Agence France-Presse – Jiji Press|url-status=live|archive-url = https://web.archive.org/web/20130330142043/http://www.japantimes.co.jp/news/2013/03/28/world/safer-vaccine-created-without-virus/#.VcLHxGCPKM_|archive-date = 30 March 2013}}</ref>

Principles that govern the immune response can now be used in tailor-made vaccines against many noninfectious human diseases, such as cancers and autoimmune disorders.<ref>{{cite journal | vauthors = Spohn G, Bachmann MF | title = Exploiting viral properties for the rational design of modern vaccines | journal = Expert Review of Vaccines | volume = 7 | issue = 1 | pages = 43–54 | date = February 2008 | pmid = 18251693 | doi = 10.1586/14760584.7.1.43 | s2cid = 40130001 }}</ref> For example, the experimental vaccine [[CYT006-AngQb]] has been investigated as a possible treatment for [[hypertension|high blood pressure]].<ref>{{cite journal | vauthors = Samuelsson O, Herlitz H | title = Vaccination against high blood pressure: a new strategy | journal = Lancet | volume = 371 | issue = 9615 | pages = 788–789 | date = March 2008 | pmid = 18328909 | doi = 10.1016/S0140-6736(08)60355-4 | s2cid = 38323966 }}</ref> Factors that affect the trends of vaccine development include progress in translatory medicine, [[demographics]], [[Regulatory Science|regulatory science]], political, cultural, and social responses.<ref>{{cite journal | vauthors = Poland GA, Jacobson RM, Ovsyannikova IG | title = Trends affecting the future of vaccine development and delivery: the role of demographics, regulatory science, the anti-vaccine movement, and vaccinomics | journal = Vaccine | volume = 27 | issue = 25–26 | pages = 3240–3244 | date = May 2009 | pmid = 19200833 | pmc = 2693340 | doi = 10.1016/j.vaccine.2009.01.069 }}</ref>

===Plants as bioreactors for vaccine production===
The idea of vaccine production via [[transgenic plants]] was identified as early as 2003. Plants such as [[tobacco]], [[potato]], [[tomato]], and [[banana]] can have genes inserted that cause them to produce vaccines usable for humans.<ref name="pmid12531364">{{cite journal | vauthors = Sala F, Manuela Rigano M, Barbante A, Basso B, Walmsley AM, Castiglione S | title = Vaccine antigen production in transgenic plants: strategies, gene constructs and perspectives | journal = Vaccine | volume = 21 | issue = 7–8 | pages = 803–808 | date = January 2003 | pmid = 12531364 | doi = 10.1016/s0264-410x(02)00603-5 }}</ref> In 2005, bananas were developed that produce a human vaccine against [[hepatitis B]].<ref>{{cite journal | vauthors = Kumar GB, Ganapathi TR, Revathi CJ, Srinivas L, Bapat VA | title = Expression of hepatitis B surface antigen in transgenic banana plants | journal = Planta | volume = 222 | issue = 3 | pages = 484–493 | date = October 2005 | pmid = 15918027 | doi = 10.1007/s00425-005-1556-y | bibcode = 2005Plant.222..484K | s2cid = 23987319 }}</ref>

== Vaccine hesitancy ==
[[File:202003- Cumulative county COVID-19 death rates - by share of votes for Donald Trump.svg |thumb|After the December 2020 introduction of COVID vaccines in the United States, a partisan gap in death rates developed, indicating the effects of vaccine skepticism.<ref name=NYTimes_20240311/> As of March 2024, more than 30 percent of Republicans had not received a COVID-19 vaccine, compared with less than 10 percent of Democrats.<ref name=NYTimes_20240311>{{cite news |last1=Leonhardt |first1=David |title=The Fourth Anniversary of the Covid Pandemic |url=https://www.nytimes.com/2024/03/11/briefing/covid-pandemic-anniversary.html |newspaper=The New York Times |date=11 March 2024 |archive-url=https://archive.today/20240311124758/https://www.nytimes.com/2024/03/11/briefing/covid-pandemic-anniversary.html |archive-date=11 March 2024 |url-status=live }} "Data excludes Alaska. Sources: C.D.C. Wonder; Edison Research. (Chart) By The New York Times. Source credits chart to Ashley Wu.</ref>]]
[[Vaccine hesitancy]] is a delay in acceptance, or refusal of vaccines despite the availability of vaccine services. The term covers outright refusals to vaccinate, delaying vaccines, accepting vaccines but remaining uncertain about their use, or using certain vaccines but not others.<ref>{{Cite journal |last=The Lancet Child & Adolescent Health |year=2019 |title=Vaccine hesitancy: a generation at risk |journal=The Lancet |volume=3 |issue=5 |page=281 |doi=10.1016/S2352-4642(19)30092-6 |pmid=30981382 |s2cid=115201206|doi-access=free }}</ref><ref name="Smith2015">{{Cite journal |last=Smith |first=MJ |date=November 2015 |title=Promoting Vaccine Confidence |journal=Infectious Disease Clinics of North America |type=Review |volume=29 |issue=4 |pages=759–69 |doi=10.1016/j.idc.2015.07.004 |pmid=26337737}}</ref><ref name="Larson2014">{{Cite journal |last1=Larson |first1=HJ |last2=Jarrett |first2=C |last3=Eckersberger |first3=E |last4=Smith |first4=DM |last5=Paterson |first5=P |date=April 2014 |title=Understanding vaccine hesitancy around vaccines and vaccination from a global perspective: a systematic review of published literature, 2007–2012. |journal=Vaccine |volume=32 |issue=19 |pages=2150–59 |doi=10.1016/j.vaccine.2014.01.081 |pmid=24598724}}</ref><ref>{{Cite journal |last1=Cataldi |first1=Jessica |last2=O'Leary |first2=Sean |date=2021 |title=Parental vaccine hesitancy: scope, causes, and potential responses |url=https://journals.lww.com/co-infectiousdiseases/Fulltext/2021/10000/Parental_vaccine_hesitancy__scope,_causes,_and.19.aspx |journal=Current Opinion in Infectious Diseases |volume=34 |issue=5 |pages=519–526 |doi=10.1097/QCO.0000000000000774 |pmid=34524202 |s2cid=237437018 |access-date=24 June 2022 |archive-date=24 December 2023 |archive-url=https://web.archive.org/web/20231224041931/https://journals.lww.com/co-infectiousdiseases/abstract/2021/10000/parental_vaccine_hesitancy__scope,_causes,_and.19.aspx |url-status=live |url-access=subscription }}</ref> There is an overwhelming [[scientific consensus]] that vaccines are generally safe and effective.<ref>{{Cite journal |date=October 2017 |title=Communicating science-based messages on vaccines |journal=Bulletin of the World Health Organization |volume=95 |issue=10 |pages=670–71 |doi=10.2471/BLT.17.021017 |pmc=5689193 |pmid=29147039}}</ref><ref>{{Cite news |title=Why do some people oppose vaccination? |work=Vox |url=https://www.vox.com/2018/8/21/17588104/vaccine-opposition-anti-vaxxer |access-date=26 November 2018 |archive-date=21 September 2019 |archive-url=https://web.archive.org/web/20190921013342/https://www.vox.com/2018/8/21/17588104/vaccine-opposition-anti-vaxxer |url-status=live }}</ref><ref>{{Cite news |last=Ceccarelli |first=Leah |name-list-style=vanc |title=Defending science: How the art of rhetoric can help |work=The Conversation |url=http://theconversation.com/defending-science-how-the-art-of-rhetoric-can-help-68210 |access-date=26 November 2018 |archive-date=5 November 2019 |archive-url=https://web.archive.org/web/20191105052610/https://theconversation.com/defending-science-how-the-art-of-rhetoric-can-help-68210 |url-status=live }}</ref><ref>{{Cite web |last=U.S. Department of Health and Human Services |title=Vaccines.gov |url=https://www.vaccines.gov/basics/safety/index.html |access-date=5 August 2018 |website=Vaccines.gov |archive-date=13 March 2019 |archive-url=https://web.archive.org/web/20190313190815/https://www.vaccines.gov/basics/safety/index.html |url-status=live }}</ref> Vaccine hesitancy often results in disease [[outbreak]]s and deaths from [[vaccine-preventable diseases]].<ref>{{Cite web |title=Frequently Asked Questions (FAQ) |url=http://www.childrenshospital.org/centers-and-services/division-of-infectious-diseases/faq-resurgence-of-measles |archive-url=https://web.archive.org/web/20131017113035/http://www.childrenshospital.org/centers-and-services/division-of-infectious-diseases/faq-resurgence-of-measles |archive-date=17 October 2013 |access-date=11 February 2014 |website=[[Boston Children's Hospital]]}}</ref><ref name="auto1">{{Cite journal |vauthors=Phadke VK, Bednarczyk RA, Salmon DA, Omer SB |date=March 2016 |title=Association Between Vaccine Refusal and Vaccine Preventable Diseases in the United States: A Review of Measles and Pertussis |journal=JAMA |volume=315 |issue=11 |pages=1149–58 |doi=10.1001/jama.2016.1353 |pmc=5007135 |pmid=26978210}}</ref><ref name="wolfesharp">{{Cite journal |vauthors=Wolfe R, Sharp L |year=2002 |title=Anti-vaccinationists past and present |url=http://bmj.bmjjournals.com/cgi/content/full/325/7361/430 |journal=BMJ |volume=325 |issue=7361 |pages=430–32 |doi=10.1136/bmj.325.7361.430 |pmc=1123944 |pmid=12193361 |access-date=14 January 2008 |archive-date=25 August 2006 |archive-url=https://web.archive.org/web/20060825024043/http://bmj.bmjjournals.com/cgi/content/full/325/7361/430 |url-status=live }}</ref><ref name="AgeOld">{{Cite journal |vauthors=Poland GA, Jacobson RM |date=January 2011 |title=The age-old struggle against the antivaccinationists |journal=The New England Journal of Medicine |volume=364 |issue=2 |pages=97–99 |doi=10.1056/NEJMp1010594 |pmid=21226573 |s2cid=39229852 }}</ref><ref>{{Cite magazine |last=Wallace A |date=19 October 2009 |title=An epidemic of fear: how panicked parents skipping shots endangers us all |url=https://www.wired.com/magazine/2009/10/ff_waronscience/all/1 |magazine=Wired |access-date=21 October 2009 |archive-date=25 December 2013 |archive-url=https://web.archive.org/web/20131225110404/http://www.wired.com/magazine/2009/10/ff_waronscience/all/1 |url-status=live }}</ref><ref>{{Cite journal |vauthors=Poland GA, Jacobson RM |date=March 2001 |title=Understanding those who do not understand: a brief review of the anti-vaccine movement |journal=Vaccine |volume=19 |issue=17–19 |pages=2440–45 |doi=10.1016/S0264-410X(00)00469-2 |pmid=11257375 |s2cid=1978650}}</ref> The [[World Health Organization]] therefore characterized vaccine hesitancy as one of the top ten global health threats in 2019.<ref>{{Cite web |title=Ten threats to global health in 2019 |url=https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019/ |archive-url=https://web.archive.org/web/20190627025209/http://www.who.int/emergencies/ten-threats-to-global-health-in-2019 |archive-date=27 June 2019 |access-date=9 December 2020 |website=[[World Health Organization]] (WHO) | url-status=live }}</ref><ref>{{Cite news |last=Georgiou |first=Aristos |date=15 January 2019 |title=Anti-vax Movement Listed by World Health Organization as One of the Top 10 Health Threats for 2019 |url=https://www.newsweek.com/world-health-organization-who-un-global-health-air-pollution-anti-vaxxers-1292493 |access-date=16 January 2019 |archive-date=22 November 2019 |archive-url=https://web.archive.org/web/20191122050616/https://www.newsweek.com/world-health-organization-who-un-global-health-air-pollution-anti-vaxxers-1292493 |url-status=live }}</ref>

==References==
{{reflist}}

== Further reading ==
* {{cite book | publisher = U.S. [[Centers for Disease Control and Prevention]] (CDC) | title = Epidemiology and Prevention of Vaccine-Preventable Diseases | veditors = Hall E, Wodi AP, Hamborsky J, Morelli V, Schillie S | edition = 14th | location = Washington D.C. | year = 2021 | url=https://www.cdc.gov/vaccines/pubs/pinkbook/index.html }}

==External links==
<!-- PLEASE see [[Wikipedia:External links]] and [[Wikipedia:Spam]]. -->

{{wikiquote|Vaccines}}
{{external media
| float  = right
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| video1 = [https://www.youtube.com/watch?v=mq-PgsVY-VU Modern Vaccine and Adjuvant Production and Characterization], [[Gen. Eng. Biotechnol. News|Genetic Engineering & Biotechnology News]]
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* [https://www.emro.who.int/entity/vpi/index.html Immunization, vaccine preventable diseases and polio transition] [[World Health Organization]]
* [https://www.who.int/teams/immunization-vaccines-and-biologicals/policies/position-papers WHO Vaccine Position Papers] [[World Health Organization]]
* [https://historyofvaccines.org/ The History of Vaccines], from the [[College of Physicians of Philadelphia]]
*: This website was highlighted by ''Genetic Engineering & Biotechnology News'' in its "Best of the Web" section in January 2015. See: {{small|{{cite news | title=The History of Vaccines | department=Best of the Web | volume=35 | issue=2 | date=15 January 2015 | page=38 | work=[[Gen. Eng. Biotechnol. News|Genetic Engineering & Biotechnology News]] }}}}

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