Live attenuated influenza vaccine

Medical uses

The live attenuated influenza vaccine is used to provide protection against the flu, caused by infection with influenza viruses.

Contraindications

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

• Children under, due to increased risk of wheezing
• Individuals with a history of hypersensitivity to previous influenza vaccination
• Individuals with a history of hypersensitivity, especially anaphylactic reactions, to eggs, egg proteins, gentamicin, gelatin, or arginine or to any other ingredient in the formulation
• 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 disease
• 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 system
• Children less than with a history of recurrent wheezing
• Children or adolescents receiving aspirin
• People with a history of syndrome, a rare disorder of the nervous system
• Pregnant women
• People who have a severe allergy to chicken eggs or who are allergic to any of the nasal spray vaccine components

Production

The live attenuated vaccine is based on a flu strain that does not cause disease, that replicates well at relatively cold temperatures (about 25 °C, 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 sucrosegradient, then packaged with sucrose, phosphate, glutamate, arginine, and hydrolyzed pig gelatin.

Risks

Even though the virus in the live attenuated influenza vaccine(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. LAIV is recommended only for people , and people who have a weakened immune system, pregnant women, and people with certain chronic diseases may not be eligible to receive the vaccine. In contrast, inactivated virus vaccines contain no living virus, and cannot cause a liveinfection. Persons receiving LAIV 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).

History

The live attenuated influenza vaccine(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 Health(NIH) in the1990s. MedImmune purchased Aviron in 2002, and the USFood and Drug Administration(FDA) approved LAIV in June2003.

The FDA initially approved LAIV only for healthy people aged 5to 49 because of concerns over possible side effects. LAIV is approved and recommended for healthychildren andolder. TheFDA approved the unfrozen refrigeratedversion for the same age group (ages 5–49) in August2006, following completion of phaseIII clinical trials.

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 fluseason, 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 fourmillion doses produced its first year on the market, despite a comparative shortage of fluvaccine in fall2004. The price was sharply lowered the next year, and MedImmune reported distributing 1.6million doses in2005. Because of the price drop, despite selling almost threetimes as many doses in2005, the company reported $21million in revenue from FluMist sales, compared to $48million the previous year.

Society and culture

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, and the brand name Fluenz Tetra in the UK and European Union. For the 2010–2011 fluseason, FluMist was the only live attenuated influenza vaccine approved by theFDA for use in theUS. All other FDA-approved lots were inactivated virus vaccines. In September2009, a live attenuated influenza vaccine for the novel H1N1 influenza virus was approved and the seasonal intranasal vaccine was approved by the European Medicines Agency(EMA) for use in the European Union in 2011. The quadrivalent vaccine version was approved for use in the European Union in2013.

, the only other company holding live attenuated influenza vaccine rights is BioDiem ofAustralia. 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.

It was the first and, , the only live attenuated vaccine for influenza available outside of Europe. In September2009, a live attenuated influenza vaccine for the novelH1N1 influenza virus was approved. In 2011, the vaccine was approved by the European Medicines Agency(EMA) for use in the European Union under the brand name Fluenz.

AstraZeneca acquired MedImmune in2007 and retired the MedImmune name. In October2024, Time magazine named AstraZenecaFluMist (an "at-home nasal vaccine") as one of the best inventions of2024.

Legal status

In May2024, the Committee for Medicinal Products for Human Use(CHMP) of the European Medicines Agency(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. The applicant for this medicinal product is AstraZenecaAB.

In September 2024, the USFDA approved FluMist for self- or caregiver-administration. TheFDA granted the approval of FluMist to MedImmuneLLC.

Research

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.

In June2006, the USNational Institutes of Health(NIH) began enrolling participants in a Phase I H5N1 study of an intranasal influenza vaccine candidate based on MedImmune's live, attenuated vaccine technology.

In September2006, the USNational Institute of Allergy and Infectious Diseases(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. Attenuated live viruses were found protective against H5N1 in mice and chickens in a 2009study.

"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) "[V]accine formulas inducing heterosubtypic T cell–mediated immunity may confer broad protection against avian and human influenza A viruses."

Notes

References

References

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