Live attenuated influenza vaccine

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Live attenuated influenza vaccine (LAIV) is a type of influenza vaccine in the form of a nasal spray that is recommended for the prevention of influenza.Template:Zwj<ref name="Flumist FDA label" />Template:Zwj<ref name="cite pmid|18662737">Template:Cite journal</ref>

It is an attenuated live vaccine, unlike other influenza vaccines, which are inactivated vaccines. Template:Abbr is administered intranasally,Template:Zwj<ref name="cite pmid|17301299">Template:Cite journal</ref> while inactivated vaccines are administered by intramuscular injection. Template:Abbr is sold under the brand names FluMist and FluMist Quadrivalent in the United States; and the brand name Fluenz Tetra in the European Union.Template:Zwj<ref name="FDA Flumist Quadrivalent">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Template:Zwj<ref name="Fluenz Tetra EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> FluMist was first introduced inTemplate:Nbsp2003 by MedImmune.Template:Zwj<ref name="FDA Statement">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Template:Zwj<ref name="approval">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="FluMist FDA archive">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In the United States, FluMist is approved for self- or caregiver-administration.Template:Zwj<ref name="FDA PR 20240920">{{#invoke:citation/CS1|citation |CitationClass=web }} Template:PD-notice</ref>Template:Zwj<ref>Template:Cite news</ref> It is the first influenzaTemplate:Nbspvaccine that does not need to be administered by a health care provider.Template:Zwj<ref name="FDA PR 20240920" />

Medical uses

The live attenuated influenza vaccine is used to provide protection against the flu, caused by infection with influenza viruses.Template:Zwj<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Template:Zwj<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Template:Zwj<ref name="FDA Flumist">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Contraindications

The use of the live attenuated influenza vaccine is contraindicated, and it should therefore not be used, in the following populations:

• Children underTemplate:NbspTemplate:Val, due to increased risk of wheezingTemplate:Zwj<ref name="Flumist Canadian Product Monograph">Template:Cite book</ref>
• Individuals with a history of hypersensitivity to previous influenza vaccinationTemplate:Zwj<ref name="Flumist Canadian Product Monograph" />
• Individuals with a history of hypersensitivity, especially anaphylactic reactions, to eggs, egg proteins, gentamicin, gelatin, or arginine or to any other ingredient in the formulationTemplate:Zwj<ref name="Flumist Canadian Product Monograph" />
• People with a medical condition that places them at high risk for complications from influenza, including those with chronic heart or lung disease, such as asthma or reactive airways diseaseTemplate:Zwj<ref name="QandA">{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref>

• People with medical conditions such as diabetes or kidney failure or people with illnesses that weaken the immune system, or who take medications that can weaken the immune systemTemplate:Zwj<ref name="QandA" />
• Children less thanTemplate:NbspTemplate:Val with a history of recurrent wheezingTemplate:Zwj<ref name="QandA" />
• Children or adolescents receiving aspirinTemplate:Zwj<ref name="QandA" />
• People with a history of [[Guillain–Barré syndrome|Template:Langr syndrome]], a rare disorder of the nervous systemTemplate:Zwj<ref name="QandA" />
• Pregnant womenTemplate:Zwj<ref name="QandA" />
• People who have a severe allergy to chicken eggs or who are allergic to any of the nasal spray vaccine componentsTemplate:Zwj<ref name="QandA" />

Production

The live attenuated vaccine is based on a flu strain that does not cause disease, that replicates well at relatively cold temperatures (about Template:Convert, for incubation purposes), and replicates poorly at body temperature (which minimizes risk to humans). Genes that code for surface proteins (targeted antigens) are combined with this host using genetic reassortment from strains that are projected to be circulating widely in the coming months. The resulting viruses are then incubated in chicken eggs and chick kidney cells. To make the refrigerated version, the virus is purified in centrifuges through a sucroseTemplate:Nbspgradient, then packaged with sucrose, phosphate, glutamate, arginine, and hydrolyzed pig gelatin.Template:Zwj<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Risks

Even though the virus in the live attenuated influenza vaccineTemplate:Nbsp(LAIV) is attenuated (low in virulence), it is still a living virus, and may cause an infection with complications in people with weakened immune systems or other underlying medical conditions. Template:Abbr is recommended only for people Template:Val, and people who have a weakened immune system, pregnant women, and people with certain chronic diseases may not be eligible to receive the vaccine.Template:Zwj<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In contrast, inactivated virus vaccines contain no living virus, and cannot cause a liveTemplate:Nbspinfection. Persons receiving Template:Abbr may shed small amounts of the vaccine virus during the first week. People coming in contact with the vaccinated person are not considered to be at risk, unless their immune systems are severely weakened (for example, bone marrow transplant recipients).Template:Zwj<ref name="cite pmid|18662737" />

History

The live attenuated influenza vaccineTemplate:Nbsp(LAIV) was developed by the University of Michigan School of Public Health in Ann Arbor, Michigan and later by Aviron, in Mountain View, California, under the sponsorship of the National Institutes of HealthTemplate:Nbsp(NIH) in theTemplate:Nbsp1990s. MedImmune purchased Aviron in 2002, and the USTemplate:NbspFood and Drug AdministrationTemplate:Nbsp(FDA) approved Template:Abbr in JuneTemplate:Nbsp2003.Template:Zwj<ref>Template:Cite news</ref>Template:Zwj<ref name="FluMist FDA archive" />

The FDA initially approved Template:Abbr only for healthy people aged 5Template:Nbspto 49 because of concerns over possible side effects. Template:Abbr is approved and recommended for healthyTemplate:Nbspchildren Template:Val andTemplate:Nbspolder. TheTemplate:NbspFDA approved the unfrozen refrigeratedTemplate:Nbspversion for the same age group (ages 5–49) in AugustTemplate:Nbsp2006, following completion of [[Phase III clinical trials|phaseTemplate:NbspIII clinical trials]].Template:Zwj<ref name="Drug Week">Template:Cite news</ref>

The cold-adapted version of the vaccine is called CAIV-T, and is stable for storage in a refrigerator, rather than requiring freezer storage as did the originally-approved formulation. Approved for the 2007-2008 fluTemplate:Nbspseason,Template:Zwj<ref name="FluMist FDA archive" /> the refrigerated formulation can be distributed more cheaply, making it more price-competitive with injected vaccines. The higher price hampered sales of the original frozen version of FluMist; FluMist was initially priced higher than injectable vaccines, and sold only 500,000 of the fourTemplate:Nbspmillion doses produced its first year on the market, despite a comparative shortage of fluTemplate:Nbspvaccine in fallTemplate:Nbsp2004.Template:Zwj<ref>Template:Cite newsTemplate:Dead linkTemplate:Cbignore</ref> The price was sharply lowered the next year, and MedImmune reported distributing 1.6Template:Nbspmillion doses inTemplate:Nbsp2005.Template:Zwj<ref>Template:Cite news</ref> Because of the price drop, despite selling almost threeTemplate:Nbsptimes as many doses inTemplate:Nbsp2005, the company reported $21Template:Nbspmillion in revenue from FluMist sales,Template:ZwjTemplate:NoteTag compared to $48Template:Nbspmillion the previous year.Template:Zwj<ref>Template:Cite news</ref>Template:ZwjTemplate:NoteTag

Society and culture

File:Flumist Home Vaccine Kit.jpg

An example of a Flumist home influenza vaccine kit, featuring unpacking and administration instructions, safety warnings, and the box containing the vaccine itself. The kit is shipped in a styrofoam cooler with cold packs to maintain the vaccine at a refrigerated temperature (not shown).

MedImmune is one company that manufactures the live attenuated influenza vaccine, which it sells under the brand name FluMist in the United States, Canada, and Japan,Template:Zwj<ref>Template:Cite news</ref> and the brand name Fluenz Tetra in the UK and European Union.Template:Zwj<ref name="Fluenz Tetra EPAR" /> For the 2010–2011 fluTemplate:Nbspseason, FluMist was the only live attenuated influenza vaccine approved by theTemplate:NbspFDA for use in theTemplate:NbspUS.Template:Zwj<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Template:Zwj<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> All other FDA-approved lots were inactivated virus vaccines.Template:ZwjTemplate:Citation needed In SeptemberTemplate:Nbsp2009, a live attenuated influenza vaccine for the novel H1N1 influenza virus was approvedTemplate:Zwj<ref name="CDC-AH1N1" /> and the seasonal intranasal vaccine was approved by the European Medicines AgencyTemplate:Nbsp(EMA) for use in the European Union in 2011.Template:Zwj<ref name="Fluenz EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The quadrivalent vaccine version was approved for use in the European Union inTemplate:Nbsp2013.Template:Zwj<ref name="Fluenz Tetra EPAR" />

Template:As of,Template:Update inline the only other company holding live attenuated influenza vaccine rights is BioDiem ofTemplate:NbspAustralia.Template:Zwj<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> BioDiem licensed rights to private production of the vaccine in China to Changchun BCHT Biotechnology, which also holds public rights for production in China sublicensed from the World Health Organization.Template:Zwj<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

It was the first and, Template:As of, the only live attenuated vaccine for influenza available outside of Europe.Template:Zwj<ref>Template:Cite journal</ref> In SeptemberTemplate:Nbsp2009, a live attenuated influenza vaccine for the novelTemplate:NbspH1N1 influenza virus was approved.Template:Zwj<ref name="CDC-AH1N1">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 2011, the vaccine was approved by the European Medicines AgencyTemplate:Nbsp(EMA) for use in the European Union under the brand name Fluenz.Template:Zwj<ref name="Fluenz EPAR" />Template:Zwj<ref>Template:Cite press release</ref>

AstraZeneca acquired MedImmune inTemplate:Nbsp2007 and retired the MedImmune name.Template:Zwj<ref>Template:Cite press release</ref>Template:Zwj<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In OctoberTemplate:Nbsp2024, Time magazine named AstraZenecaTemplate:NbspFluMist (an "at-home nasal vaccine") as one of the best inventions ofTemplate:Nbsp2024.Template:Zwj<ref>Template:Cite magazine</ref>

Legal status

In MayTemplate:Nbsp2024, the Committee for Medicinal Products for Human UseTemplate:Nbsp(CHMP) of the European Medicines AgencyTemplate:Nbsp(EMA) adopted a positive opinion, recommending the granting of a marketing authorization for Fluenz, intended for the prevention of influenza disease in children and adolescents.Template:Zwj<ref name="Fluenz EPAR 2" />Template:Zwj<ref>Template:Cite press release</ref> The applicant for this medicinal product is AstraZenecaTemplate:NbspAB.Template:Zwj<ref name="Fluenz EPAR 2">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In September 2024, the USTemplate:NbspFDA approved FluMist for self- or caregiver-administration. TheTemplate:NbspFDA granted the approval of FluMist to MedImmuneTemplate:NbspLLC.Template:Zwj<ref name="FDA PR 20240920" />

Research

Template:Update The live attenuated influenza vaccine is designed to be quickly modifiable to present the surface antigens of seasonal flu. This modifiability could also allow it to be quickly customized as a vaccine against a pandemic influenza if one were to emerge. In light of the global spread of H5N1, ways of reducing human mortality in the event of an H5N1 pandemic have been investigated. Modifying FluMist to serve as a specific human H5N1 vaccine is among the measures studied.Template:Zwj<ref>Template:Cite journal</ref>

In JuneTemplate:Nbsp2006, the USTemplate:NbspNational Institutes of HealthTemplate:Nbsp(NIH) began enrolling participants in a Phase I H5N1 study of an intranasal influenza vaccine candidate based on MedImmune's live, attenuated vaccine technology.Template:Zwj<ref>Template:Cite press release</ref>

In SeptemberTemplate:Nbsp2006, the USTemplate:NbspNational Institute of Allergy and Infectious DiseasesTemplate:Nbsp(NIAID) reported that inoculation with a live attenuated influenza vaccine modified to present surface antigens of certain H5N1 variants provided broad protection against other H5N1 variants in mouse and ferret models.Template:Zwj<ref>Template:Cite journal Template:Open access</ref> Attenuated live viruses were found protective against H5N1 in mice and chickens in a 2009Template:Nbspstudy.Template:Zwj<ref>Template:Cite journal</ref>

"Several trials have reported that live attenuated influenza vaccines can boost virus-specific CTLs as well as mucosal and serum antibodies and provide broad cross-protection against heterologous human influenza A viruses." (58, 59)Template:Zwj<ref name="ReferenceA">Template:Cite journal</ref> "[V]accine formulas inducing heterosubtypic T cell–mediated immunity may confer broad protection against avian and human influenza A viruses."Template:Zwj<ref name="ReferenceA" />