Live attenuated influenza vaccine

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Live attenuated influenza vaccine
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Nurse administering the FluMist product
Vaccine description
Target Influenza
Vaccine type Attenuated
Clinical data
Trade names Flumist, Flumist Quadrivalent, Fluenz Tetra
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administration 		Intranasal
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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. [2] [7]

Contents

It is an attenuated live vaccine, unlike other influenza vaccines, which are inactivated vaccines. Live attenuated influenza vaccine is administered intranasally, [8] while inactivated vaccines are administered by intramuscular injection. Live attenuated influenza vaccine is sold under the brand names FluMist and FluMist Quadrivalent in the United States; and the brand name Fluenz Tetra in the European Union. [4] [6] FluMist was first introduced in 2003 by MedImmune. [9] [10] [11]

In the United States, FluMist is approved for self- or caregiver-administration. [12] It is the first influenza vaccine that does not need to be administered by a health care provider. [12]

Medical uses

The live attenuated influenza vaccine is used to provide protection against the flu caused by infection with influenza viruses. [13] [14] [3]

Contraindications

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

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 sucrose gradient, then packaged with sucrose, phosphate, glutamate, arginine, and gelatin made from pigs that has been hydrolyzed with acid. [17]

Risks

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. [18] 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. [7]

History

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. [19] [11]

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. [20]

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, [11] 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. [21] The price was sharply lowered the next year, and the company reported distributing 1.6 million doses in 2005. [22] 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. [23]

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, [24] and the brand name Fluenz Tetra [6] 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. [25] [26] 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 [27] and the seasonal intranasal vaccine was approved by the European Medicines Agency (EMA) for use in the European Union in 2011. [5] The quadrivalent version was approved for use in the European Union in 2013. [6]

As of 2007, the only other company holding live attenuated influenza vaccine rights is BioDiem of Australia. [28] 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. [29]

It was the first and, as of 2007, the only live attenuated vaccine for influenza available outside of Europe. [30] In September 2009, a live attenuated influenza vaccine for the novel H1N1 influenza virus was approved. [27] In 2011, the vaccine was approved by the European Medicines Agency (EMA) for use in the European Union under the brand name Fluenz. [5] [31]

AstraZeneca acquired MedImmune and retired the MedImmune name. [32] [33]

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. [34] [35] The applicant for this medicinal product is AstraZeneca AB. [34]

In September 2024, the US FDA approved FluMist (Influenza Vaccine Live, Intranasal) for self- or caregiver-administration. [12] The FDA granted the approval of FluMist to MedImmune LLC. [12]

Research

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. [36]

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. [37]

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. [38] Attenuated live viruses were found protective against H5N1 in mice and chickens in a 2009 study. [39]

"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) [40] "[V]accine formulas inducing heterosubtypic T cell–mediated immunity may confer broad protection against avian and human influenza A viruses." [40]

Related Research Articles

<span class="mw-page-title-main">Influenza A virus subtype H5N1</span> Subtype of influenza A virus

Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the influenza A virus, which causes influenza (flu), predominantly in birds. It is enzootic in many bird populations, and also panzootic. A/H5N1 virus can also infect mammals that have been exposed to infected birds; in these cases, symptoms are frequently severe or fatal.

<span class="mw-page-title-main">Influenza vaccine</span> Vaccine against influenza

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.

<span class="mw-page-title-main">MedImmune</span> Biopharmaceutical company, acquired by AstraZeneca in 2007

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.

<span class="mw-page-title-main">Influenza pandemic</span> Pandemic involving influenza

An influenza pandemic is an epidemic of an influenza virus that spreads across a large region and infects a large proportion of the population. There have been six major influenza epidemics in the last 140 years, with the 1918 flu pandemic being the most severe; this is estimated to have been responsible for the deaths of 50–100 million people. The 2009 swine flu pandemic resulted in under 300,000 deaths and is considered relatively mild. These pandemics occur irregularly.

<span class="mw-page-title-main">Transmission and infection of H5N1</span> Spread of an influenza virus

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.

<i>Influenza B virus</i> Species of virus

Influenza B virus is the only species in the genus Betainfluenzavirus in the virus family Orthomyxoviridae.

<span class="mw-page-title-main">H5N1 vaccine clinical trials</span> Clinical trials of influenza vaccine

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.

<span class="mw-page-title-main">NS1 influenza protein</span>

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), formerly referred to as NS2 protein, which mediates the export of influenza virus ribonucleoprotein (RNP) complexes from the nucleus into the cytoplasm, where they are assembled.

<span class="mw-page-title-main">Influenza</span> Infectious disease

Influenza, commonly known as "the flu" or just "flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms begin one to four days after exposure to the virus and last for about two to eight days. Diarrhea and vomiting can occur, particularly in children. Influenza may progress to pneumonia from the virus or a subsequent bacterial infection. Other complications include acute respiratory distress syndrome, meningitis, encephalitis, and worsening of pre-existing health problems such as asthma and cardiovascular disease.

<span class="mw-page-title-main">Adenovirus vaccine</span>

An adenovirus vaccine is a vaccine against adenovirus infection. According to American CDC, "There is currently no adenovirus vaccine available to the general public.

<span class="mw-page-title-main">2009 swine flu pandemic vaccine</span> Protection against the H1N1/09 virus

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.

<span class="mw-page-title-main">H5N1 vaccine</span> Vaccine designed to provide immunity against H5N1 influenza

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.

<span class="mw-page-title-main">Novavax</span> American biotechnology company

Novavax, Inc. is an American biotechnology company based in Gaithersburg, Maryland, that develops vaccines to counter serious infectious diseases. Prior to 2020, company scientists developed experimental vaccines for influenza and respiratory syncytial virus (RSV), as well as Ebola and other emerging infectious diseases. During 2020, the company redirected its efforts to focus on development and approval of its NVX-CoV2373 vaccine for COVID-19.

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.

<span class="mw-page-title-main">Viral vector vaccine</span> Type of vaccine

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.

<span class="mw-page-title-main">Polyvalent influenza vaccine</span> Vaccine against multiple flu strains

Polyvalent influenza vaccine is a type of influenza vaccine that provides immunity against more than one type of antigen. In the second week after receiving the flu shot, the body's immune system is triggered by the antigens so the body starts producing antibodies. These antibodies help fight against influenza viruses. Influenza symptoms and deaths can be prevented by getting an influenza vaccine every year. Currently circulating influenza strains that can cause seasonal epidemics include influenza A viruses, which can be further divided into subtype A(H1N1) and A(H3N2), and influenza B viruses.

References

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  2. 1 2 "Flumist- influenza vaccine live intranasal spray". DailyMed. 6 August 2024. Retrieved 21 September 2024.
  3. 1 2 "FluMist". U.S. Food and Drug Administration (FDA). 17 April 2019. STN: 125020. Archived from the original on 23 June 2022. Retrieved 22 June 2022.
  4. 1 2 "FluMist Quadrivalent". U.S. Food and Drug Administration (FDA). 15 November 2019. STN 125020. Archived from the original on 28 November 2019. Retrieved 28 November 2019.
  5. 1 2 3 "Fluenz EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 31 July 2020. Retrieved 9 April 2020.
  6. 1 2 3 4 "Fluenz Tetra EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 28 November 2019. Retrieved 27 November 2019.
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  8. ↑ Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M, et al. (CAIV-T Comparative Efficacy Study Group) (February 2007). "Live attenuated versus inactivated influenza vaccine in infants and young children". The New England Journal of Medicine. 356 (7): 685–696. doi: 10.1056/NEJMoa065368 . PMID   17301299.
  9. ↑ "FDA Information Regarding FluMist Quadrivalent Vaccine". U.S. Food and Drug Administration (FDA). 16 January 2018. Archived from the original on 28 November 2019. Retrieved 27 November 2019.
  10. ↑ Midthun K, Masiello S (17 July 2003). "CBER Approval Letter, Influenza Virus Vaccine, Live, Intranasal (FluMist)". U.S. Food and Drug Administration (FDA). Archived from the original on 29 September 2007. Retrieved 6 July 2008.
  11. 1 2 3 "FluMist". U.S. Food and Drug Administration (FDA). Archived from the original on 22 July 2017. Retrieved 10 April 2020.
  12. 1 2 3 4 "FDA Approves Nasal Spray Influenza Vaccine for Self- or Caregiver-Administration". U.S. Food and Drug Administration. 20 September 2024. Retrieved 21 September 2024.PD-icon.svg This article incorporates text from this source, which is in the public domain .
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  14. ↑ "Live Attenuated Influenza Vaccine. The Nasal Spray Flu Vaccine". Centers for Disease Control and Prevention (CDC). 15 October 2021. Archived from the original on 14 October 2019. Retrieved 22 June 2022.
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  17. ↑ FDA Vaccines and Related Biological Products Advisory Committee (April 2007). "FluMist Live, Attenuated Influenza Vaccine Briefing Document" (PDF). Food and Drug Administration . Archived from the original (PDF) on 26 January 2018.
  18. ↑ "Facts and Myths about FluMist". AstraZeneca. September 2020. Archived from the original on 11 November 2020. Retrieved 10 November 2020.
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  20. ↑ "MedImmune begins shipping live intranasal flu vaccine for 2006-2007 after U.S. FDA release". Lab Law Weekly. 25 August 2006. Archived from the original on 14 July 2011. Retrieved 6 July 2008.
  21. ↑ Rosenwald M (6 January 2005). "FluMist Sales Falling Short, Survey Finds". The Washington Post . p. E05. Retrieved 6 July 2008.[ dead link ]
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  23. ↑ Rosenwald M (3 February 2006). "Sales of MedImmune's Flu Vaccine Drop Sharply". The Washington Post . p. D04. Archived from the original on 23 October 2016. Retrieved 6 July 2008.
  24. ↑ biopharma-reporter.com (17 July 2023). "FluMist Quadrivalent 'unlikely' to see great success in Japan". biopharma-reporter.com. Retrieved 6 May 2024.
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  29. ↑ "BioDiem licenses LAIV technology to Changchun BCHT". ResearchInChina. 10 February 2012. Archived from the original on 21 October 2013. Retrieved 21 October 2013.
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  31. ↑ "European Commission approves nasal spray vaccine Fluenz for the prevention of seasonal influenza in children". AstraZeneca (Press release). 1 February 2011. Archived from the original on 13 June 2022. Retrieved 29 August 2022.
  32. ↑ "AstraZeneca Ships FluMist Quadrivalent Vaccine in the US for 2020-2021 Flu Season" (Press release). AstraZeneca. 13 August 2020. Archived from the original on 9 July 2021. Retrieved 8 July 2021– via Business Wire.
  33. ↑ "AstraZeneca retires Medimmune name amid sales turnaround". BioPharma Dive. 14 February 2019. Archived from the original on 9 July 2021. Retrieved 8 July 2021.
  34. 1 2 "Fluenz EPAR". European Medicines Agency. 21 May 2024. Retrieved 1 June 2024.
  35. ↑ "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 27-30 May 2024". European Medicines Agency (Press release). 31 May 2024. Retrieved 13 June 2024.
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  37. ↑ "MedImmune and National Institutes of Health Begin Clinical Testing of a Live, Attenuated Intranasal Vaccine Against an H5N1 Avian Influenza Virus". phx.corporate-ir.net (Press release). 15 June 2006. Archived from the original on 9 January 2016. Retrieved 22 June 2022.
  38. ↑ Suguitan AL, McAuliffe J, Mills KL, Jin H, Duke G, Lu B, et al. (September 2006). "Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets". PLOS Medicine. 3 (9): e360. doi: 10.1371/journal.pmed.0030360 . PMC   1564176 . PMID   16968127. Open Access logo PLoS transparent.svg
  39. ↑ Steel J, Lowen AC, Pena L, Angel M, Solórzano A, Albrecht R, et al. (February 2009). "Live attenuated influenza viruses containing NS1 truncations as vaccine candidates against H5N1 highly pathogenic avian influenza". Journal of Virology. 83 (4): 1742–1753. doi:10.1128/JVI.01920-08. PMC   2643794 . PMID   19073731.
  40. 1 2 Lee LY, Ha D, Simmons C, de Jong MD, Chau NV, Schumacher R, et al. (October 2008). "Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals". The Journal of Clinical Investigation. 118 (10): 3478–3490. doi:10.1172/JCI32460. PMC   2542885 . PMID   18802496.
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