View source for Vaccinia

{{Short description|Strain of poxvirus}}
{{about|the virus related to smallpox vaccines|the plant genus|Vaccinium}}
{{distinguish|vaccine}}
{{Virusbox
| image = Vaccinia virus PHIL 2143 lores.jpg
| image_alt = A TEM micrograp of Vaccinia virus virions
| image_caption = A [[Transmission electron microscopy|TEM]] [[micrograph]] of Vaccinia virus [[virion]]s
| parent = Orthopoxvirus
| species = Orthopoxvirus vaccinia
| subdivision_ranks = Member viruses
| subdivision_ref = <ref>{{cite web |title=ICTV 9th Report (2011) ''Poxviridae'' |url=https://ictv.global/report_9th/dsDNA/poxviridae |website=International Committee on Taxonomy of Viruses (ICTV) |access-date=17 December 2018 |language=en |archive-date=8 August 2022 |archive-url=https://web.archive.org/web/20220808033034/https://ictv.global/report_9th/dsDNA/poxviridae |url-status=live }}</ref>
| subdivision = * [[Buffalopox virus]]
* [[Cantagalo virus]]
* [[Rabbitpox virus Utrecht]]
* [[Vaccinia virus Ankara]]
* [[Vaccinia virus Copenhagen]]
* [[Vaccinia virus WR]]
}}
{{Infobox medical condition (new)
| name            = Vaccinia
| specialty    =virology
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| types           = [[Progressive vaccinia]]
| causes          =
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}}
The '''vaccinia virus''' ('''VACV''' or '''VV'''){{Efn|Taxonomical species names were updated by the [[International Committee on Taxonomy of Viruses]] in June 2024, with ''Vaccinia virus'' being renamed '''''Orthopoxvirus vaccinia'''''.<ref>{{Cite web |title=Taxon Details {{!}} ICTV |url=https://ictv.global/taxonomy/taxondetails?taxnode_id=202304775&taxon_name=Orthopoxvirus%20vaccinia |access-date=2024-08-30 |website=ictv.global}}</ref>}} is a large, complex, [[Viral envelope|enveloped]] [[virus]] belonging to the [[poxvirus]] family.<ref name=Sherris>{{cite book | veditors = Ryan KJ, Ray CG | title = Sherris Medical Microbiology | edition = 4th | publisher = McGraw Hill | year = 2004 | isbn = 978-0-8385-8529-0 }}</ref> It has a [[linear DNA|linear]], [[double-stranded DNA|double-stranded]] [[DNA]] [[genome]] approximately 190 [[base pair|kbp]] in length, which encodes approximately 250 [[gene]]s. The dimensions of the [[virion]] are roughly 360 × 270 × 250&nbsp;[[nanometer|nm]], with a mass of approximately 5–10 [[Femtogram|fg]].<ref>{{Cite journal| first1 = L.| first2 = A. K.| first3 = A.| first4 = D.| first5 = R.| title = Characterization of vaccinia virus particles using microscale silicon cantilever resonators and atomic force microscopy| journal = Sensors and Actuators B Chemical| volume = 115| issue = 1| pages = 189–197| last1 = Johnson| year = 2006| doi = 10.1016/j.snb.2005.08.047| last2 =  Gupta| last3 =  Ghafoor| last4 =  Akin| last5 =  Bashir| bibcode = 2006SeAcB.115..189J}}</ref> The vaccinia virus is the source of the modern [[smallpox vaccine]], which the [[World Health Organization]] (WHO) used to eradicate smallpox in a global vaccination campaign in 1958–1977. Although ''smallpox'' no longer exists in the wild, ''vaccinia'' virus is still studied widely by scientists as a tool for [[gene therapy]] and [[genetic engineering]].

[[Smallpox]] had been an endemic human disease that had a 30% fatality rate. {{source?|date=July 2025}} In 1796, the British doctor [[Edward Jenner]] proved that an infection with the relatively mild [[cowpox]] virus would also confer immunity to the deadly smallpox. Jenner referred to cowpox as ''variolae vaccinae'' (smallpox of the cow). However, the origins of the smallpox vaccine became murky over time,<ref>{{cite book |last1=Baxby |first1=Derrick |title=Jenner's Smallpox Vaccine: The Riddle of Vaccinia Virus and Its Origin |date=1981 |publisher=Heinemann Educational Books |isbn=978-0-435-54057-9 |language=en}}</ref> especially after [[Louis Pasteur]] developed laboratory techniques for creating vaccines in the 19th century. [[Allan Watt Downie]] demonstrated in 1939 that the modern smallpox vaccine was serologically distinct from cowpox,<ref name="downie1939"/> and ''vaccinia'' was subsequently recognized as a separate viral species. Whole-genome sequencing has revealed that ''vaccinia'' is most closely related to [[horsepox]], and the cowpox strains found in Great Britain are the ''least'' closely related to ''vaccinia''.<ref name="carroll2011">{{cite journal |last1=Carroll |first1=Darin S. |last2=Emerson |first2=Ginny L. |last3=Li |first3=Yu |last4=Sammons |first4=Scott |last5=Olson |first5=Victoria |last6=Frace |first6=Michael |last7=Nakazawa |first7=Yoshinori |last8=Czerny |first8=Claus Peter |last9=Tryland |first9=Morten |last10=Kolodziejek |first10=Jolanta |last11=Nowotny |first11=Norbert |last12=Olsen-Rasmussen |first12=Melissa |last13=Khristova |first13=Marina |last14=Govil |first14=Dhwani |last15=Karem |first15=Kevin |last16=Damon |first16=Inger K. |last17=Meyer |first17=Hermann |title=Chasing Jenner's Vaccine: Revisiting Cowpox Virus Classification |journal=PLOS ONE |date=8 August 2011 |volume=6 |issue=8 |article-number=e23086 |doi=10.1371/journal.pone.0023086 |pmid=21858000 |pmc=3152555 |bibcode=2011PLoSO...623086C |language=en |issn=1932-6203|doi-access=free }}</ref>

== Classification of vaccinia infections ==
In addition to the morbidity of uncomplicated primary vaccination, transfer of infection to other sites by scratching, and  post-vaccinial [[encephalitis]], other complications of vaccinia infections may be divided into the following types:<ref name="Andrews">{{cite book |author1=James, William D. |author2=Berger, Timothy G. |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=978-0-7216-2921-6 |display-authors=etal}}</ref>{{Rp|391}}
* [[Generalized vaccinia]]
* [[Eczema vaccinatum]]
* [[Progressive vaccinia]] (vaccinia gangrenosum, vaccinia necrosum)
* [[Roseola vaccinia]]

==Origin==
Vaccinia virus is closely related to the virus that causes [[cowpox]]; historically the two were often considered to be one and the same.<ref name=Huygelen>{{cite journal |author=Huygelen C |title=Jenner's cowpox vaccine in light of current vaccinology |language=nl |journal=Verh. K. Acad. Geneeskd. Belg. |volume=58 |issue=5 |pages=479–536; discussion 537–538 |year=1996 |pmid=9027132 }}</ref> The precise origin of vaccinia virus is unknown due to the lack of record-keeping, as the virus was repeatedly cultivated and [[Serial passage|passaged]] in research laboratories for many decades.<ref name=Henderson_1999>{{cite book | vauthors = Henderson DA, Moss B | veditors = Plotkin SA, Orenstein WA | title = Vaccines | orig-year = 1988 | edition = 3rd | year = 1999 | publisher = WB Saunders | location = Philadelphia, Pennsylvania | isbn = 978-0-7216-7443-8 | chapter = Smallpox and Vaccinia | chapter-url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=vacc.chapter.3 | access-date = 2017-09-17 | archive-date = 2009-06-01 | archive-url = https://web.archive.org/web/20090601172056/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=vacc.chapter.3 | url-status = live }}</ref> The most common notion is that vaccinia virus, cowpox virus, and [[variola]] virus (the causative agent of smallpox) were all derived from a common ancestral virus. There is also speculation that vaccinia virus was originally isolated from [[horse]]s,<ref name=Huygelen /> and analysis of DNA from an early (1902) sample of smallpox vaccine showed that it was 99.7% similar to horsepox virus.<ref>{{cite journal|doi= 10.1056/NEJMc1707600|pmid= 29020595|title= An Early American Smallpox Vaccine Based on Horsepox|journal= New England Journal of Medicine|volume= 377|issue= 15|pages= 1491–1492|year= 2017|last1= Schrick|first1= Livia|last2= Tausch|first2= Simon H|last3= Dabrowski|first3= P. Wojciech|last4= Damaso|first4= Clarissa R|last5= Esparza|first5= José|last6= Nitsche|first6= Andreas|doi-access= free}}</ref>

==Virology==
Poxviruses are unique among [[DNA virus]]es because they [[DNA replication|replicate]] only in the [[cytoplasm]] of the [[Host (biology)|host cell]], outside of the [[cell nucleus|nucleus]].<ref>{{cite journal |vauthors=Tolonen N, Doglio L, Schleich S, Krijnse Locker J |title=Vaccinia Virus DNA Replication Occurs in Endoplasmic Reticulum-enclosed Cytoplasmic Mini-Nuclei |journal=Mol. Biol. Cell |volume=12 |issue=7 |pages=2031–46 |date=1 July 2001|pmid=11452001 |pmc=55651 |doi=10.1091/mbc.12.7.2031 }}</ref> Therefore, the large genome is required for encoding various [[enzymes]] and proteins involved in viral DNA replication and gene [[transcription (genetics)|transcription]]. During its replication cycle, VV produces four infectious forms which differ in their outer [[cell membrane|membranes]]: intracellular mature virion (IMV), the intracellular enveloped virion (IEV), the cell-associated enveloped virion (CEV) and the extracellular enveloped virion (EEV).<ref>{{cite journal |vauthors=[[Geoffrey L. Smith|Smith GL]], Vanderplasschen A, Law M |title=The formation and function of extracellular enveloped Vaccinia virus |journal=J. Gen. Virol. |volume=83 |issue=Pt 12 |pages=2915–31 |date=1 December 2002 |pmid=12466468 |doi=10.1099/0022-1317-83-12-2915 |doi-access=free }}</ref> Although the issue remains contentious, the prevailing view is that the IMV consists of a single [[lipoprotein]] membrane, while the CEV and EEV are both surrounded by two membrane layers and the IEV has three envelopes. The IMV is the most abundant infectious form and is thought to be responsible for spread between hosts. On the other hand, the CEV is believed to play a role in cell-to-cell spread and the EEV is thought to be important for long range dissemination within the host organism.{{citation needed|date=May 2021}}

==Multiplicity reactivation==
Vaccinia virus is able to undergo multiplicity reactivation (MR).<ref name=Abel>{{cite journal |author=ABEL P |title=Multiplicity reactivation and marker rescue with vaccinia virus |journal=Virology |volume=17 |issue= 4|pages=511–9 |date=August 1962 |pmid=13858909 |doi= 10.1016/0042-6822(62)90150-2}}</ref> MR is the process by which two, or more, virus genomes containing otherwise lethal damage interact within an infected cell to form a viable virus genome.  Abel<ref name=Abel /> found that vaccinia viruses  exposed to doses of UV light sufficient to prevent progeny formation when single virus particles infected host chick embryo cells, could still produce viable progeny viruses when host cells were infected by two or more of these inactivated viruses; that is, MR could occur.  Kim and Sharp demonstrated MR of vaccinia virus after treatment with UV-light,<ref>{{cite journal |vauthors=Sharp DG, Kim KS |title=Multiplicity reactivation and radiation survival of aggregated vaccinia virus. Calculation of plaque titer based on MR and particle aggregation seen in the electron microscope |journal=Virology |volume=29 |issue=3 |pages=359–66 |date=July 1966 |pmid=5922451 |doi= 10.1016/0042-6822(66)90211-X}}</ref> nitrogen mustard,<ref>{{cite journal |vauthors=Kim KS, Sharp DG |title=Multiplicity reactivation of vaccinia virus particles treated with nitrogen mustard |journal=J. Virol. |volume=1 |issue=1 |pages=45–9 |date=February 1967 |pmid=5623957 |pmc=375503 |doi= 10.1128/JVI.1.1.45-49.1967}}</ref> and X-rays or gamma rays.<ref>{{cite journal |vauthors=Kim KS, Sharp DG |title=Multiplicity reactivation of gamma- and x-irradiated Vaccinia virus in L cells |journal=Radiat. Res. |volume=33 |issue=1 |pages=30–6 |date=January 1968 |pmid=5634978 |doi= 10.2307/3572239|jstor=3572239 |bibcode=1968RadR...33...30K }}</ref>  Michod et al.<ref>{{cite journal |vauthors=Michod RE, Bernstein H, Nedelcu AM | year = 2008 | title = Adaptive value of sex in microbial pathogens | journal = Infect Genet Evol | volume = 8 | issue = 3| pages = 267–285 | doi = 10.1016/j.meegid.2008.01.002 | pmid=18295550| bibcode = 2008InfGE...8..267M }}</ref> reviewed numerous examples of MR in different viruses, and suggested that MR is a common form of sexual interaction in viruses that provides the advantage of recombinational repair of genome damages.{{additional citation needed|date=May 2021}}

==Host resistance==
Vaccinia contains within its genome genes for several [[protein]]s that give the virus resistance to [[interferon]]s:
* K3L ({{PDBe-KB|P18378}}) is a protein with [[Homology (biology)|homology]] to the protein ''[[eIF-2|eukaryotic initiation factor 2]]'' (eIF-2alpha). K3L protein inhibits the action of [[Protein kinase R|PKR]], an activator of interferons.<ref name=Davies1993/>
* E3L ({{UniProt|P21605}}) is another protein encoded by Vaccinia. E3L also inhibits PKR activation, and is also able to bind to double stranded RNA.<ref name=Davies1993>{{cite journal |vauthors=Davies MV, Chang HW, Jacobs BL, Kaufman RJ |title=The E3L and K3L vaccinia virus gene products stimulate translation through inhibition of the double-stranded RNA-dependent protein kinase by different mechanisms |journal=J. Virol. |volume=67 |issue=3 |pages=1688–1692 |date=1 March 1993|pmid=8094759 |pmc=237544 |doi=10.1128/JVI.67.3.1688-1692.1993 }}</ref>
* B18R ({{UniProt|P21076}}) directly binds to type I interferon to abolish its function; in other words it works as a decoy receptor. It is used in bioengineering, for cells with added nucleic acid might otherwise enter an antiviral state that reduces protein output.<ref>{{cite journal |last1=Kim |first1=Yuriy G. |last2=Baltabekova |first2=Aliya Zh. |last3=Zhiyenbay |first3=Erzhan E. |last4=Aksambayeva |first4=Altynai S. |last5=Shagyrova |first5=Zhadyra S. |last6=Khannanov |first6=Rinat |last7=Ramanculov |first7=Erlan M. |last8=Shustov |first8=Alexandr V. |title=Recombinant Vaccinia virus-coded interferon inhibitor B18R: Expression, refolding and a use in a mammalian expression system with a RNA-vector |journal=PLOS ONE |date=7 December 2017 |volume=12 |issue=12 |article-number=e0189308 |doi=10.1371/journal.pone.0189308|doi-access=free |pmid=29216299 |pmc=5720773 |bibcode=2017PLoSO..1289308K }}</ref> It is also used in a [[Moderna]] paper to enhance the chance of converting a cell into a [[induced pluripotent stem cell]] (iPSC) using mRNA.<ref name=rossi10a>{{cite journal |doi=10.1016/j.stem.2010.08.012 |title=Highly Efficient Reprogramming to Pluripotency and Directed Differentiation of Human Cells with Synthetic Modified mRNA |year=2010 |last1=Warren |first1=Luigi |last2=Manos |first2=Philip D. |last3=Ahfeldt |first3=Tim |last4=Loh |first4=Yuin-Han |last5=Li |first5=Hu |last6=Lau |first6=Frank |last7=Ebina |first7=Wataru |last8=Mandal |first8=Pankaj K. |last9=Smith |first9=Zachary D. |last10=Meissner |first10=Alexander |last11=Daley |first11=George Q. |last12=Brack |first12=Andrew S. |last13=Collins |first13=James J. |last14=Cowan |first14=Chad |last15=Schlaeger |first15=Thorsten M. |last16=Rossi |first16=Derrick J. |journal=Cell Stem Cell |volume=7 |issue=5 |pages=618–630 |pmid=20888316 |pmc=3656821 }}</ref>


==Treatments==

Dissemination of vaccinia infection is rare due widespread immunization.<ref name="VerardiTitong">{{cite journal |last1=Verardi |first1=Paulo H. |last2=Titong |first2=Allison |last3=Hagen |first3=Caitlin J. |title=A vaccinia virus renaissance: New vaccine and immunotherapeutic uses after smallpox eradication |journal=Human Vaccines & Immunotherapeutics |date=July 2012 |volume=8 |issue=7 |pages=961–970 |doi=10.4161/hv.21080 |pmid=22777090 |pmc=3495727 }}</ref> Immunocompromised patients may be at risk of developing severe infection. The only current FDA-approved treatment is [[antiserum|serotherapy]] (intravenous infusion of anti-anti-vaccinia immunoglobulin).<ref name="LinkTscherne2025">{{cite journal |last1=Link |first1=Ellen K. |last2=Tscherne |first2=Alina |last3=Sutter |first3=Gerd |last4=Smith |first4=Emily R. |last5=Gurwith |first5=Marc |last6=Chen |first6=Robert T. |last7=Volz |first7=Asisa |title=A Brighton collaboration standardized template with key considerations for a benefit/risk assessment for a viral vector vaccine based on a non-replicating modified vaccinia virus Ankara viral vector |journal=Vaccine |date=January 2025 |volume=43 |issue=Pt 1 |article-number=126521 |doi=10.1016/j.vaccine.2024.126521 |pmid=39612556 |doi-access=free }}</ref>

==Use as a vaccine==
[[Image:Smallpox vaccine site.jpg|thumb|right|150px|Site of a vaccinia injection, several days later.]]
Vaccinia virus infection is typically very mild and often does not cause symptoms in healthy individuals, although it may cause rash and [[fever]]. Immune responses generated from a vaccinia virus infection protects the person against a lethal [[smallpox]] infection. For this reason, vaccinia virus was, and still is, being used as a live-virus vaccine against smallpox. Unlike vaccines that use weakened forms of the virus being vaccinated against, the vaccinia virus vaccine cannot cause a smallpox infection because it does not contain the smallpox virus. However, certain complications and/or vaccine adverse effects occasionally arise. The chance of this happening is significantly increased in people who are [[immunocompromised]]. Approximately 1 to 2 people out of every 1 million people vaccinated could die as a result of life-threatening reactions to the [[vaccination]].<ref>{{cite web |url=https://www.cdc.gov/smallpox/vaccine-basics/vaccination-effects.html |title=Side Effects of Smallpox Vaccination {{!}} Smallpox {{!}} CDC |date=2017-07-12 |access-date=2022-05-25 |archive-date=2022-05-26 |archive-url=https://web.archive.org/web/20220526103938/https://www.cdc.gov/smallpox/vaccine-basics/vaccination-effects.html |url-status=live }}</ref> The rate of myopericarditis with ACAM2000 is 5.7 per 1,000 of primary vaccinees.<ref>{{cite journal |url=https://www.cdc.gov/mmwr/volumes/71/wr/mm7122e1.htm?s_cid=mm7122e1_w |title=Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination {{!}} Smallpox {{!}} CDC |journal=MMWR. Morbidity and Mortality Weekly Report |date=2022-06-03 |volume=71 |doi=10.15585/mmwr.mm7122e1 |last1=Rao |first1=Agam K. |last2=Petersen |first2=B. W. |last3=Whitehill |first3=F. |last4=Razeq |first4=J. H. |last5=Isaacs |first5=S. N. |last6=Merchlinsky |first6=M. J. |last7=Campos-Outcalt |first7=D. |last8=Morgan |first8=R. L. |last9=Damon |first9=I. |last10=Sánchez |first10=P. J. |last11=Bell |first11=B. P. |issue=22 |pages=734–742 |pmid=35653347 |pmc=9169520 |access-date=2022-08-08 |archive-date=2022-08-08 |archive-url=https://web.archive.org/web/20220808033646/https://www.cdc.gov/mmwr/volumes/71/wr/mm7122e1.htm?s_cid=mm7122e1_w |url-status=live }}</ref>

On September 1, 2007, the U.S. [[Food and Drug Administration]] (FDA) licensed a new [[vaccine]] [[ACAM2000]] against [[smallpox]] which can be produced quickly upon need. Manufactured by [[Sanofi Pasteur]], the U.S. [[Centers for Disease Control and Prevention]] stockpiled 192.5 million doses of the new vaccine (see list of common strains below).<ref>{{cite news |url=https://www.chron.com/news/nation-world/article/FDA-approves-new-smallpox-vaccine-1833591.php |title=FDA approves new smallpox vaccine |last=Heilprin |first=John |agency=AP |website=Houston Chronicle |date=1 September 2007 |access-date=25 May 2018 |archive-date=26 May 2018 |archive-url=https://web.archive.org/web/20180526185953/https://www.chron.com/news/nation-world/article/FDA-approves-new-smallpox-vaccine-1833591.php |url-status=live }}</ref>

A smallpox vaccine, [[Imvanex]], which is based on the [[Modified vaccinia Ankara]] strain, was approved by the [[European Medicines Agency]] (EMA) in 2013.<ref>{{cite web|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002596/human_med_001666.jsp&mid=WC0b01ac058001d124|title=European public assessment report summary: Imvanex|date=2018-09-17|access-date=2014-05-19|archive-date=2018-06-20|archive-url=https://web.archive.org/web/20180620154521/http://www.ema.europa.eu/ema//index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F002596%2Fhuman_med_001666.jsp&mid=WC0b01ac058001d124|url-status=dead}}</ref> This strain has been used in vaccines during the [[2022 monkeypox outbreak]].{{cn|date=November 2022}}

''Vaccinia'' is also used in recombinant [[vaccines]], as a vector for expression of foreign genes within a host, in order to generate an immune response. Other [[Poxviridae|poxviruses]] are also used as live recombinant vaccines.<ref>{{cite journal |last1=Vanderplasschen |first1=A. |last2=Pastoret |first2=P.-P. |title=The Uses of Poxviruses as Vectors |journal=Current Gene Therapy |volume=3 |number=6 |date=December 2003 |pages=583–595 |doi=10.2174/1566523034578168|pmid=14683453 }}</ref>

==History==
The original vaccine for smallpox, and the origin of the idea of vaccination, was [[Cowpox]], described by [[Edward Jenner]] in 1798. The [[Latin]] term used for Cowpox was ''Variolae vaccinae'',  Jenner's own translation of "smallpox of the cow".  That term lent its name to the whole idea of vaccination.<ref>{{cite journal|pmid=9987167|year=1999|last1=Baxby|first1=D| author-link = Derrick Baxby|title=Edward Jenner's Inquiry; a bicentenary analysis|volume=17|issue=4|pages=301–307|journal=Vaccine|doi=10.1016/S0264-410X(98)00207-2}}</ref>  When it was realized that the virus used in smallpox vaccination was not, or was no longer, the same as cowpox virus, the name 'vaccinia' was used for the virus in smallpox vaccine. (See OED.) Vaccine potency and efficacy prior to the invention of refrigerated methods of transportation was unreliable. The vaccine would be rendered impotent by heat and sunlight, and the method of drying samples on quills and shipping them to countries in need often resulted in an inactive vaccine. Another method employed was the "arm to arm" method. This involved vaccinating an individual then transferring it to another as soon as the infectious pustule forms, then to another, etc. This method was used as a form of living transportation of the vaccine, and usually employed orphans as carriers. However, this method was problematic due to the possibility of spreading other blood diseases, such as hepatitis and syphilis, as was the case in 1861, when 41 Italian children contracted syphilis after being vaccinated by the "arm to arm" method.<ref>{{cite book |last=Tucker |first=Jonathan B. |title=Scourge: The Once and Future Threat of Smallpox |place=New York |publisher=Grove/Atlantic Inc. |date=2001}}</ref> [[Henry Austin Martin]] introduced a method for vaccine production from calves.<ref>{{Cite journal|last1=Esparza|first1=José|last2=Lederman|first2=Seth|last3=Nitsche|first3=Andreas|last4=Damaso|first4=Clarissa R.|date=2020-06-19|title=Early smallpox vaccine manufacturing in the United States: Introduction of the "animal vaccine" in 1870, establishment of "vaccine farms", and the beginnings of the vaccine industry|journal=Vaccine|volume=38|issue=30|pages=4773–4779|doi=10.1016/j.vaccine.2020.05.037|issn=0264-410X|pmc=7294234|pmid=32473878}}</ref>

In 1913, E. Steinhardt, C. Israeli, and R. A. Lambert grew vaccinia virus in fragments of pig [[cornea]]l [[tissue culture]].<ref name="Steinhardt_1913">{{cite journal | vauthors = Steinhardt E, Israeli C, Lambert RA | title = Studies on the cultivation of the virus of vaccinia | journal = J Inf Dis | volume = 13 | issue = 2 | pages = 294–300 | date = September 1913 | doi = 10.1093/infdis/13.2.294 | jstor = 30073371 | url = https://zenodo.org/record/1431761 | access-date = 2019-09-11 | archive-date = 2022-03-31 | archive-url = https://web.archive.org/web/20220331193944/https://zenodo.org/record/1431761 | url-status = live }}</ref>[[File:Smallpox vaccine USP.jpg|left|thumb|1950s US smallpox vaccine, produced by the National Drug Company in Philadelphia from ''vaccinia''<ref>{{Cite web |title=Tube for smallpox vaccine with two sealed needles |url=https://collections.thackraymuseum.co.uk/object-474-058 |access-date=2024-05-29 |website=Thackray Museum of Medicine Collections Online |id=474.058 |archive-date=2024-05-29 |archive-url=https://web.archive.org/web/20240529135512/https://collections.thackraymuseum.co.uk/object-474-058 |url-status=live }}</ref>]]A paper published in 1915 by Fredrick W. Twort, a student of Willian Bulloch, is considered to be the beginning of modern phage research. He was attempting to grow vaccinia virus on agar media in the absence of living cells when he noted that many colonies of contaminating micrococci grew up and appeared mucoid, watery or glassy, and this transformation could be induced in other colonies by inoculation of the fresh colony with material from the watery colony. Using a microscope, he observed that bacteria had degenerated into small granules that stained red with [[Giemsa stain]]. He concluded that "...it [the agent of transformation] might almost be considered as an acute infectious disease of micrococci."<ref>{{Cite book|title=Phages : their role in bacterial pathogenesis and biotechnology|date=2005|publisher=ASM Press |editor=Waldor, Matthew K. |editor2=Friedman, David I. |editor3=Adhya, Sankar Lal |isbn=1-55581-307-0|location=Washington, D.C.|oclc=57557385}}</ref>
In 1939  [[Allan Watt Downie]] showed that the smallpox vaccines being used in the 20th century and cowpox virus were not the same, but were immunologically related.<ref name="downie1939">{{cite journal|pmc=2065307|year=1939|last1=Downie|first1=AW|title=The Immunological Relationship of the Virus of Spontaneous Cowpox to Vaccinia Virus|volume=20|issue=2|pages=158–176|journal=British Journal of Experimental Pathology}}</ref><ref>{{Cite journal | last1 = Tyrrell | first1 = D. A. J. | last2 = McCarthy | first2 = K. | doi = 10.1098/rsbm.1990.0004 | title = Allan Watt Downie. September 1901 – 26 January 1988 | journal = [[Biographical Memoirs of Fellows of the Royal Society]] | volume = 35 | pages = 98–112 | year = 1990 | title-link = Allan Watt Downie | pmid = 11622284 | doi-access = free }}</ref>

===2000–present===
In March 2007, a 2-year-old Indiana boy and his mother contracted a life-threatening vaccinia infection from the boy's father.<ref name=MMWR>{{cite journal |author=[[Centers for Disease Control and Prevention]] (CDC) |title=Household transmission of vaccinia virus from contact with a military smallpox vaccinee—Illinois and Indiana, 2007 |journal=[[Morbidity and Mortality Weekly Report]] |volume=56 |issue=19 |pages=478–81 |year=2007 |pmid=17510612 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5619a4.htm?s_cid=mm5619a4_e |access-date=2017-09-17 |archive-date=2021-03-10 |archive-url=https://web.archive.org/web/20210310190959/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5619a4.htm?s_cid=mm5619a4_e |url-status=live }}</ref> The boy developed the telltale rash over 80 percent of his body after coming into close contact with his father, who was vaccinated for smallpox before being deployed overseas by the [[United States Army]]. The United States military resumed smallpox vaccinations in 2002. The child acquired the infection due to [[eczema]], which is a known risk factor for vaccinia infection. The boy was treated with [[intravenous immunoglobulin]], [[cidofovir]], and [[Tecovirimat]] (ST-246), a (then) experimental drug developed by [[SIGA Technologies]].<ref>{{cite press release | title = SIGA's Smallpox Drug Candidate Administered to Critically Ill Human Patient | publisher = SIGA Technologies | date = 2007-03-17 | url = https://investor.siga.com/node/7346 | access-date = 2018-07-20 | archive-date = 2018-07-20 | archive-url = https://web.archive.org/web/20180720195253/https://investor.siga.com/node/7346 | url-status = dead }}</ref> On April 19, 2007, he was sent home with no after effects except for possible scarring of the skin.<ref name=MMWR/>

In 2010, the [[Centers for Disease Control and Prevention]] (CDC) reported that a woman in Washington had contracted vaccinia virus infection after digital vaginal contact with her boyfriend, a military member who had recently been vaccinated for smallpox. The woman had a history of childhood eczema, but she had not been symptomatic as an adult. The CDC indicated that it was aware of four similar cases in the preceding 12 months of vaccinia infection after sexual contact with a recent military vaccinee.<ref name=MMWR2>{{cite journal |author=[[Centers for Disease Control and Prevention]] (CDC) |title=Vaccinia Virus Infection After Sexual Contact with a Military Smallpox Vaccinee—Washington, 2010 |journal=[[Morbidity and Mortality Weekly Report]] |volume=59 |issue=25 |pages=773–75 |year=2010 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5925a2.htm?s_cid=mm5925a2_w |pmid=20592687 |access-date=2017-09-17 |archive-date=2021-04-23 |archive-url=https://web.archive.org/web/20210423104514/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5925a2.htm?s_cid=mm5925a2_w |url-status=live }}</ref> Further cases—also in patients with a history of eczema—occurred in 2012.<ref name=MMWR3>{{cite journal |author=[[Centers for Disease Control and Prevention]] (CDC) |title=Secondary and tertiary transmission of vaccinia virus after sexual contact with a smallpox vaccinee—San Diego, California, 2012 |journal=[[Morbidity and Mortality Weekly Report]] |volume=62 |issue=8 |pages=145–7 |date=March 2013 |pmid=23446513 |pmc=4604863 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6208a2.htm |access-date=2017-09-17 |archive-date=2021-03-09 |archive-url=https://web.archive.org/web/20210309193408/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6208a2.htm |url-status=live }}</ref>

==Common strains==
This is a list of some of the well-characterized vaccinia strains used for research and vaccination.{{citation needed|date=October 2016}}
* Lister (also known as Elstree): the English vaccine strain used by [[Leslie Collier]] to develop heat stable vaccine in powdered form. Used as the basis for vaccine production during the World Health Organization Smallpox Eradication Campaign (SEC)
* [[Dryvax]] (also known as "Wyeth"): the vaccine strain previously used in the [[United States]], produced by [[Wyeth]]. Used in the SEC, it was replaced in 2008<ref>{{cite journal |title=Notice to Readers: Newly Licensed Smallpox Vaccine to Replace Old Smallpox Vaccine |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=57 |issue=8 |pages=207–8 |date=February 29, 2008 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5708a6.htm |access-date=September 17, 2017 |archive-date=May 20, 2022 |archive-url=https://web.archive.org/web/20220520085013/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5708a6.htm |url-status=live }}</ref> by ACAM2000 (see below), produced by Acambis. It was produced as preparations of [[calf (animal)|calf]] [[lymph]] which was [[freeze-dried]] and treated with antibiotics.
* EM63: Russian strain used in the SEC
* [[ACAM2000]]: The current strain in use in the US, produced by Acambis. ACAM2000 was derived from a [[cloning|clone]] of a Dryvax virus by [[Viral plaque|plaque purification]]. It is produced in cultures of [[Vero cells]].
* [[Modified vaccinia Ankara]] (also known as MVA): a highly attenuated (not virulent) strain created by passaging vaccinia virus several hundred times in [[chicken]] [[embryo]] [[fibroblasts]]. Unlike some other vaccinia strains it does not make [[immunodeficient]] [[Laboratory mouse|mice]] sick and therefore may be safer to use in humans who have weaker immune systems due to being very young, very old, having [[HIV/AIDS]], etc.
* LC16m8: an attenuated strain developed and currently used in Japan
* CV-1: an attenuated strain developed in the United States and used there in the late 1960s- 1970s
* Western Reserve
* Copenhagen
* Connaught Laboratories (Canada)

== See also ==
* [[B13R (virus protein)]]

== Notes ==
{{noteslist}}

== References ==
{{Reflist}}

==Further reading==
{{refbegin}}
* {{cite journal | vauthors = Gubser C, Hué S, Kellam P, [[Geoffrey L. Smith|Smith GL]] | title = Poxvirus genomes: a phylogenetic analysis | journal = J Gen Virol | date = January 2004 | volume = 85 | issue = 1 | pages = 105–17 | pmid = 14718625 | doi = 10.1099/vir.0.19565-0 | doi-access = free }}
* {{cite journal |author=[[Centers for Disease Control and Prevention]] (CDC) |title=Vulvar vaccinia infection after sexual contact with a military smallpox vaccinee—Alaska, 2006 |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=56 |issue=17 |pages=417–9 |year=2007 |pmid=17476203 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5617a1.htm |access-date=2017-09-17 |archive-date=2021-06-28 |archive-url=https://web.archive.org/web/20210628144901/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5617a1.htm |url-status=live }}
* {{cite journal|pmc=4885089|year=2016|last1=Al Ali|first1=S|title=Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors|journal=Viruses|volume=8|issue=5|page=134|last2=Baldanta|first2=S|last3=Fernández-Escobar|first3=M|last4=Guerra|first4=S|doi=10.3390/v8050134|pmid=27213433|doi-access=free}}
* {{cite journal|pmc=2440811|pmid=18612436|year=2008|last1=Rubins|first1=K. H.|title=Comparative analysis of viral gene expression programs during poxvirus infection: A transcriptional map of the vaccinia and monkeypox genomes|journal=PLOS ONE|volume=3|issue=7|article-number=e2628|last2=Hensley|first2=L. E.|last3=Bell|first3=G. W.|last4=Wang|first4=C|last5=Lefkowitz|first5=E. J.|last6=Brown|first6=P. O.|last7=Relman|first7=D. A.|doi=10.1371/journal.pone.0002628|bibcode=2008PLoSO...3.2628R|doi-access=free}}
{{refend}}
* {{cite web   | url = https://www.ncbi.nlm.nih.gov/genome?Db=genome&Cmd=ShowDetailView&TermToSearch=18372   | publisher = National Center for Biotechnology Information   | title = Vaccinia virus, complete genome   | access-date = 2007-07-25}}
* {{ cite web
   |vauthors=Condit RC, Moussatche N, Traktman P | title = The Vaccinia Virion: 3D Tour
   | url = http://www.vacciniamodel.com
   | access-date = 2007-07-26
}}
* {{cite web   | title = Smallpox   | publisher = [[Centers for Disease Control and Prevention]]   | url = http://www.bt.cdc.gov/agent/smallpox   | work = Emergency Preparedness & Response   | access-date = 2007-07-26   | archive-url = https://web.archive.org/web/20070813192027/http://www.bt.cdc.gov/agent/smallpox/   | archive-date = 2007-08-13   | url-status = dead   }}
* {{cite web|url=https://www.bbc.com/future/article/20220725-the-mystery-virus-that-protects-against-monkeypox|title=The mystery virus that protects against monkeypox|first=Zaria|last=Gorvett|date=26 July 2022 |access-date=26 July 2022}}

== External links ==
{{Medical resources
| ICD11           = {{ICD11|1E73}}
| ICD10           = B08.0
| ICD9            = {{ICD9|051.0}}
| eMedicineSubj   = med
| eMedicineTopic  = 2356
| MeshID          = D014615
| SNOMED CT       = 111852003
}}
* [http://www.viprbrc.org/brc/home.do?decorator=pox Virus Pathogen Database and Analysis Resource (ViPR): Poxviridae]

{{Viral cutaneous conditions}}
{{Taxonbar|from=Q1986297}}
{{Authority control}}

[[Category:Vaccinia| ]]
[[Category:Chordopoxvirinae]]
[[Category:Virus-related cutaneous conditions]]
[[Category:Genetic engineering]]