![]() Nurse administering the FluMist product | |
Vaccine description | |
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Target | Influenza |
Vaccine type | Attenuated |
Clinical data | |
Trade names | Flumist Quadrivalent, Fluenz Tetra |
AHFS/Drugs.com | Monograph |
License data | |
Routes of administration | Intranasal |
ATC code | |
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Identifiers | |
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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. It was developed by the Syrian-American epidemiologist Hunein Maassab. [5]
It is an attenuated live vaccine, unlike other influenza vaccines, which are inactivated vaccines. Live attenuated influenza vaccine is administered intranasally, [6] while inactivated vaccines are administered by intramuscular injection. Live attenuated influenza vaccine is sold under the brand name FluMist Quadrivalent in the United States and the brand name Fluenz Tetra in the European Union. [7] [4] FluMist was first introduced in 2003 by MedImmune. [8] [9] [10]
The live attenuated influenza vaccine is used to provide protection against the flu caused by infection with influenza viruses. [11] [12] [13]
The use of the live attenuated influenza vaccine is contraindicated, and should therefore not be used, in the following populations:
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 sucrose gradient, then packaged with sucrose, phosphate, glutamate, arginine, and gelatin made from pigs that has been hydrolyzed with acid. [16]
Even though the virus in the live attenuated influenza vaccine 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. The live attenuated influenza vaccine is recommended only for people 2–49 years of age, and people who have a weakened immune system, pregnant women, and people with certain chronic diseases may not be eligible to receive live attenuated influenza vaccine. [17] In contrast, inactivated virus vaccines contain no living virus, and cannot cause a live infection. Persons receiving the live attenuated influenza vaccine 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) and possible recombination with other (wild or live vaccine) flu strains. [5]
The live attenuated influenza vaccine 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 the 1990s. MedImmune, Inc. purchased Aviron in 2002, and the US Food and Drug Administration (FDA) approved the live attenuated influenza vaccine in June 2003. [18] [10]
The FDA initially approved the live attenuated influenza vaccine only for healthy people aged 5 to 49 because of concerns over possible side effects. The live attenuated influenza vaccine is approved and recommended for healthy children 24 months of age and older. The FDA approved the unfrozen refrigerated version for the same age group (ages 5–49) in August 2006, following completion of phase III clinical trials. [19]
The cold-adapted influenza vaccine 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 flu season, [10] the refrigerated formulation can be distributed more economically, so that the price differential with shots (which had hampered sales of the original frozen version of FluMist) is now largely eliminated. FluMist was initially priced higher than the injectable vaccines, but sold only 500,000 of the four million doses it produced its first year on the market, despite a comparative shortage of flu vaccine in fall 2004. [20] The price was sharply lowered the next year, and the company reported distributing 1.6 million doses in 2005. [21] Because of the price drop, despite selling almost three times as many doses in 2005, the company reported $21 million in FluMist sales, compared to $48 million the previous year. [22]
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, [23] and the brand name Fluenz Tetra [4] in the UK and European Union. For the 2010–2011 flu season, FluMist was the only live attenuated influenza vaccine approved by the FDA for use in the US. [24] [25] All other FDA-approved lots were inactivated virus vaccines.[ citation needed ] In September 2009, a live attenuated influenza vaccine for the novel H1N1 influenza virus was approved [26] and the seasonal intranasal vaccine was approved by the European Medicines Agency (EMA) for use in the European Union in 2011. [3] The quadrivalent version was approved for use in the European Union in 2013. [4]
As of 2007 [update] , the only other company holding live attenuated influenza vaccine rights is BioDiem of Australia. [27] 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. [28]
It was the first and, as of 2007 [update] , the only live attenuated vaccine for influenza available outside of Europe. [29] In September 2009, a live attenuated influenza vaccine for the novel H1N1 influenza virus was approved. [26] In 2011, the vaccine was approved by the European Medicines Agency (EMA) for use in the European Union under the brand name Fluenz. [3] [30]
AstraZeneca acquired MedImmune and retired the MedImmune name. [31] [32]
In May 2024, 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 the medicinal product Fluenz, intended for the prevention of influenza disease in children and adolescents. [33] [34] The applicant for this medicinal product is AstraZeneca AB. [33]
The live attenuated influenza vaccine is designed to be quickly modifiable to present the surface antigens of seasonal flu. The 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. [35]
In June 2006, the National 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. [36]
In September 2006, the National Institute of Allergy and Infectious Diseases (NIAID) reported that inoculation with a live attenuated influenza vaccine modified to present the surface antigens of certain H5N1 variants provided broad protection against other H5N1 variants in the mouse and ferret models. [37] Attenuated live viruses were found protective against H5N1 in mice and chickens in a 2009 study. [38]
"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) [39] "[V]accine formulas inducing heterosubtypic T cell–mediated immunity may confer broad protection against avian and human influenza A viruses." [39]
Influenza A virus (IAV) is a pathogen with strains that infect birds and some mammals, as well as causing seasonal flu in humans. Mammals in which different strains of IAV circulate with sustained transmission are bats, pigs, horses and dogs; other mammals can occasionally become infected.
Avian influenza, also known as avian flu or bird flu, is a disease caused by the influenza A virus (IAV) which primarily affects birds but can sometimes affect mammals including humans. Wild aquatic birds are the primary host of Influenza A virus (IAV), which is endemic in many bird populations.
Influenza vaccines, colloquially known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies from year to year, most provide modest to high protection against influenza. Vaccination against influenza began in the 1930s, with large-scale availability in the United States beginning in 1945.
MedImmune, LLC was a wholly owned subsidiary of AstraZeneca before February 14, 2019, when it was announced that the MedImmune name and branding would be discontinued in favor of AstraZeneca.
Influenza A virus subtype H3N2 (A/H3N2) is a subtype of viruses that causes influenza (flu). H3N2 viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains. In years in which H3N2 is the predominant strain, there are more hospitalizations.
Transmission and infection of H5N1 from infected avian sources to humans has been a concern since the first documented case of human infection in 1997, due to the global spread of H5N1 that constitutes a pandemic threat.
Influenza B virus is the only species in the genus Betainfluenzavirus in the virus family Orthomyxoviridae.
H5N1 clinical trials are clinical trials concerning H5N1 vaccines, which are intended to provide immunization to influenza A virus subtype H5N1. They are intended to discover pharmacological effects and identify any adverse reactions the vaccines may achieve in humans.
The NS1 influenza protein (NS1) is a viral nonstructural protein encoded by the NS gene segments of type A, B and C influenza viruses. Also encoded by this segment is the nuclear export protein (NEP), formally referred to as NS2 protein, which mediates the export of influenza virus ribonucleoprotein (RNP) complexes from the nucleus, where they are assembled.
Pandemrix is an influenza vaccine for influenza pandemics, such as the 2009 flu pandemic. The vaccine was developed by GlaxoSmithKline (GSK) and patented in September 2006.
The 2009 swine flu pandemic vaccines were influenza vaccines developed to protect against the pandemic H1N1/09 virus. These vaccines either contained inactivated (killed) influenza virus, or weakened live virus that could not cause influenza. The killed virus was injected, while the live virus was given as a nasal spray. Both these types of vaccine were produced by growing the virus in chicken eggs. Around three billion doses were produced, with delivery in November 2009.
A H5N1 vaccine is an influenza vaccine intended to provide immunization to influenza A virus subtype H5N1.
Cell-based vaccines are developed from mammalian or more rarely avian or insect cell lines rather than the more common method which uses the cells in embryonic chicken eggs to develop the antigens. The potential use of cell culture techniques in developing viral vaccines has been widely investigated in the 2000s as a complementary and alternative platform to the current egg-based strategies.
Vaccine shedding is a form of viral shedding which can occasionally occur following a viral infection caused by an attenuated vaccine. Illness in others resulting from transmission through this type of viral shedding is rare. Most vaccines are not attenuated vaccines, and therefore cannot cause vaccine-induced viral shedding, though the idea of shedding is a popular anti-vaccination myth.
Dame Sarah Catherine Gilbert FRS is an English vaccinologist who is a Professor of Vaccinology at the University of Oxford and co-founder of Vaccitech. She specialises in the development of vaccines against influenza and emerging viral pathogens. She led the development and testing of the universal flu vaccine, which underwent clinical trials in 2011.
A nasal vaccine is a vaccine administered through the nose that stimulates an immune response without an injection. It induces immunity through the inner surface of the nose, a surface that naturally comes in contact with many airborne microbes. Nasal vaccines are emerging as an alternative to injectable vaccines because they do not use needles and can be introduced through the mucosal route. Nasal vaccines can be delivered through nasal sprays to prevent respiratory infections, such as influenza.
A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material (DNA) that can be transcribed by the recipient's host cells as mRNA coding for a desired protein, or antigen, to elicit an immune response. As of April 2021, six viral vector vaccines, four COVID-19 vaccines and two Ebola vaccines, have been authorized for use in humans.
Type A influenza vaccine is for the prevention of infection of influenza A virus and also the influenza-related complications. Different monovalent type A influenza vaccines have been developed for different subtypes of influenza A virus including H1N1 and H5N1. Both intramuscular injection or intranasal spray are available on market. Unlike the seasonal influenza vaccines which are used annually, they are usually used during the outbreak of certain strand of subtypes of influenza A. Common adverse effects includes injection site reaction and local tenderness. Incidences of headache and myalgia were also reported with H1N1 whereas cases of fever has also been demonstrated with H5N1 vaccines. It is stated that immunosuppressant therapies would reduce the therapeutic effects of vaccines and that people with egg allergy should go for the egg-free preparations.
Live recombinant vaccines are biological preparations that stimulate immune responses to a pathogen through the use of genetically modified live bacteria or viruses. These live pathogens are biologically engineered to express exogenous antigens in the cytoplasm of target cells, thereby triggering immune responses. This form of vaccine combines the beneficial features of attenuated and recombinant vaccines, providing the long-lasting immunity of attenuated vaccines’ with recombinant vaccines’ genetically engineered precision and safety.