H5N1 vaccine

Last updated
H5N1 vaccine
Clinical data
ATC code
Legal status
Legal status

A H5N1 vaccine is an influenza vaccine intended to provide immunization to influenza A virus subtype H5N1.

Contents

Vaccines have been formulated against several of the avian H5N1 influenza varieties. Vaccination of poultry against the H5N1 epizootic is widespread in certain countries. Some vaccines also exist for use in humans, and others are in testing, but none have been made available to civilian populations, however production could be scaled up to quantities sufficient to protect much of the Earth's population in the event of an H5N1 pandemic.[ citation needed ]

In January 2020, the U.S. Food and Drug Administration (FDA) approved Audenz, an adjuvanted influenza A (H5N1) monovalent vaccine. [2] [3] Audenz is a vaccine indicated for active immunization for the prevention of disease caused by the influenza A virus H5N1 subtype contained in the vaccine. Audenz is approved for use in persons six months of age and older at increased risk of exposure to the influenza A virus H5N1 subtype contained in the vaccine. [2]

Some older, egg-based H5N1 vaccines for humans that have been licensed are:

Other licensed H5N1 vaccines include:

In November 2013, the U.S. Food and Drug Administration (FDA) approved an experimental H5N1 bird flu vaccine to be held in stockpiles. [11] [12] In a clinical trial including 3,400 adults, 91% of people age 18-64 and 74% of people age 65 or older formed an immune response sufficient to provide protection. Reported adverse effects were generally mild, with pain at the injection site being the most common adverse effect. [13]

In June 2024, the European Commission signed a four-year contract with CSL Seqirus to secure 665,000 pre-pandemic vaccines with a provision for a further 40 million doses of avian flu vaccines for 15 member states. [14]

Production technologies

H5N1 continually mutates, meaning vaccines based on current samples of avian H5N1 cannot be depended upon to work in the case of a future pandemic of H5N1. While there can be some cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain. Daniel R. Lucey, co-director of the Biohazardous Threats and Emerging Diseases graduate program at Georgetown University, has made this point, "There is no H5N1 pandemic so there can be no pandemic vaccine." However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic. Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain.[ medical citation needed ]

Problems with H5N1 vaccine production include:[ medical citation needed ]

Cell culture (cell-based) manufacturing technology can be applied to influenza vaccines as they are with most viral vaccines and thereby solve the problems associated with creating flu vaccines using chicken eggs. [15]

Vaccine production capacity: The protective immune response generated by influenza vaccines is largely based on viral hemagglutinin (HA) and neuraminidase (NA) antigens in the vaccine.[ medical citation needed ] As a consequence, the basis of influenza vaccine manufacturing is growing massive quantities of virus in order to have sufficient amounts of these protein antigens to stimulate immune responses.[ medical citation needed ] Influenza vaccines used in the United States and around world have traditionally been manufactured by growing virus in fertilized hens' eggs, a commercial process that has been in place for decades.[ medical citation needed ] To achieve vaccine production targets millions of 11-day-old fertilized eggs must be available every day of production.[ medical citation needed ]
In the near term, further expansion of these systems will provide additional capacity for the U.S.-based production of both seasonal and pandemic vaccines, however, the surge capacity that will be needed for a pandemic response cannot be met by egg-based vaccine production alone, as it is impractical to develop a system that depends on hundreds of millions of 11-day-old specialized eggs on a standby basis. In addition, because a pandemic could result from an avian influenza strain that is lethal to chickens, it is impossible to ensure that eggs will be available to produce vaccine when needed.
In contrast, cell culture manufacturing technology can be applied to influenza vaccines as they are with most viral vaccines (e.g., polio vaccine, measles-mumps-rubella vaccine, chickenpox vaccine). In this system, viruses are grown in closed systems such as bioreactors containing large numbers of cells in growth media rather than eggs. The surge capacity afforded by cell-based technology is insensitive to seasons and can be adjusted to vaccine demand, as capacity can be increased or decreased by the number of bioreactors or the volume used within a bioreactor. In addition to supporting basic research on cell-based influenza vaccine development, HHS is currently supporting a number of vaccine manufacturers in the advanced development of cell-based influenza vaccines with the goal of developing U.S.-licensed cell-based influenza vaccines produced in the United States. [16] The US government has purchased from Sanofi Pasteur and Chiron Corporation several million doses of vaccine meant to be used in case of an influenza pandemic of H5N1 avian influenza and is conducting clinical trials with these vaccines. [17] Researchers at the University of Pittsburgh have had success with a genetically engineered vaccine that took only a month to make and completely protected chickens from the highly pathogenic H5N1 virus. [18] [19]

According to the United States Department of Health and Human Services:

In addition to supporting basic research on cell-based influenza vaccine development, HHS is currently supporting a number of vaccine manufacturers in the advanced development of cell-based influenza vaccines with the goal of developing U.S.-licensed cell-based influenza vaccines produced in the United States.

Dose-sparing technologies

Current U.S.-licensed vaccines stimulate an immune response based on the quantity of HA (hemagglutinin) antigen included in the dose. Methods to stimulate a strong immune response using less HA antigen are being studied in H5N1 and H9N2 vaccine trials. These include changing the mode of delivery from intramuscular to intradermal and the addition of immune-enhancing adjuvant to the vaccine formulation. Additionally, HHS is soliciting contract proposals from manufacturers of vaccines, adjuvants, and medical devices for the development and licensure of influenza vaccines that will provide dose-sparing alternative strategies. [20]

Chiron Corporation is now[ when? ] recertified and under contract with the National Institutes of Health to produce 8,000–10,000 investigational doses of Avian Flu (H5N1) vaccine. MedImmune and Aventis Pasteur are under similar contracts. [21] The United States government hopes to obtain enough vaccine in 2006 to treat 4 million people. However, it is unclear whether this vaccine would be effective against a hypothetical mutated strain that would be easily transmitted through human populations, and the shelf life of stockpiled doses has yet to be determined. [22]

The New England Journal of Medicine reported on March 30, 2006, on one of dozens of vaccine studies being conducted. [23] The Treanor et al. study was on vaccine produced from the human isolate (A/Vietnam/1203/2004 H5N1) of a virulent clade 1 influenza A (H5N1) virus with the use of a plasmid rescue system, with only the hemagglutinin and neuraminidase genes expressed and administered without adjuvant. "The rest of the genes were derived from an avirulent egg-adapted influenza A/PR/8/34 strain. The hemagglutinin gene was further modified to replace six basic amino acids associated with high pathogenicity in birds at the cleavage site between hemagglutinin 1 and hemagglutinin 2. Immunogenicity was assessed by microneutralization and hemagglutination-inhibition assays with the use of the vaccine virus, although a subgroup of samples were tested with the use of the wild-type influenza A/Vietnam/1203/2004 (H5N1) virus." The results of this study combined with others scheduled to be completed by spring 2007 is hoped will provide a highly immunogenic vaccine that is cross-protective against heterologous influenza strains. [24]

On August 18, 2006. the World Health Organization (WHO) changed the H5N1 strains recommended for candidate vaccines for the first time since 2004. "The WHO's new prototype strains, prepared by reverse genetics, include three new H5N1 subclades. The hemagglutinin sequences of most of the H5N1 avian influenza viruses circulating in the past few years fall into two genetic groups, or clades. Clade 1 includes human and bird isolates from Vietnam, Thailand, and Cambodia and bird isolates from Laos and Malaysia. Clade 2 viruses were first identified in bird isolates from China, Indonesia, Japan, and South Korea before spreading westward to the Middle East, Europe, and Africa. The clade 2 viruses have been primarily responsible for human H5N1 infections that have occurred during late 2005 and 2006, according to WHO. Genetic analysis has identified six subclades of clade 2, three of which have a distinct geographic distribution and have been implicated in human infections:

On the basis of the three subclades, the WHO is offering companies and other groups that are interested in pandemic vaccine development these three new prototype strains:

[...] Until now,[ when? ] researchers have been working on prepandemic vaccines for H5N1 viruses in clade 1. In March,[ when? ] the first clinical trial of a U.S. vaccine for H5N1 showed modest results. In May,[ when? ] French researchers showed somewhat better results in a clinical trial of an H5N1 vaccine that included an adjuvant. Vaccine experts aren't sure if a vaccine effective against known H5N1 viral strains would be effective against future strains. Although the new viruses will now be available for vaccine research, WHO said clinical trials using the clade 1 viruses should continue as an essential step in pandemic preparedness, because the trials yield useful information on priming, cross-reactivity, and cross-protection by vaccine viruses from different clades and subclades." [25] [26]

As of November 2006, the United States Department of Health and Human Services (HHS) had enough H5N1 pre-pandemic vaccine to treat about 3 million people (5.9 million full-potency doses) in spite of 0.2 million doses used for research and 1.4 million doses that have begun to lose potency (from the original 7.5 million full-potency doses purchased from Sanofi Pasteur and Chiron Corp.). The expected shelf life of seasonal flu vaccine is about a year so the fact that most of the H5N1 pre-pandemic stockpile is still good after about two years is considered encouraging. [27]

Clinical trials

H5N1 clinical trials are clinical trials concerning H5N1 vaccines. They are intended to discover pharmacological effects and identify any adverse reactions the vaccines may achieve in humans. [28]

Related Research Articles

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

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.

<span class="mw-page-title-main">Avian influenza</span> Influenza caused by viruses adapted to birds

Avian influenza, also known as avian flu or bird flu, is a disease caused by the influenza A virus, which primarily affects birds but can sometimes affect mammals including humans. Wild aquatic birds are the primary host of the influenza A virus, which is enzootic in many bird populations.

<span class="mw-page-title-main">Antigenic shift</span> Process by which two or more different strains of a virus combine to form a new subtype

Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains. The term is often applied specifically to influenza, as that is the best-known example, but the process is also known to occur with other viruses, such as visna virus in sheep. Antigenic shift is a specific case of reassortment or viral shift that confers a phenotypic change.

<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">Live attenuated influenza vaccine</span> Nasal influenza vaccine

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.

<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">Influenza A virus subtype H2N2</span> Subtype of Influenza A virus

Influenza A virus subtype H2N2 (A/H2N2) is a subtype of Influenza A virus. H2N2 has mutated into various strains including the "Asian flu" strain, H3N2, and various strains found in birds. It is also suspected of causing a human pandemic in 1889. The geographic spreading of the 1889 Russian flu has been studied and published.

<span class="mw-page-title-main">Influenza A virus subtype H3N2</span> Virus subtype

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.

<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.

<span class="mw-page-title-main">H5N1 genetic structure</span> Genetic structure 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. All subtypes of the influenza A virus share the same genetic structure and are potentially able to exchange genetic material by means of reassortment

<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">Fujian flu</span> Strains of influenza

Fujian flu refers to flu caused by either a Fujian human flu strain of the H3N2 subtype of the Influenza A virus or a Fujian bird flu strain of the H5N1 subtype of the Influenza A virus. These strains are named after Fujian, a coastal province in Southeast China.

<span class="mw-page-title-main">Human mortality from H5N1</span>

H5N1 influenza virus is a type of influenza A virus which mostly infects birds. H5N1 flu is a concern due to the its global spread that may constitute a pandemic threat. The yardstick for human mortality from H5N1 is the case-fatality rate (CFR); the ratio of the number of confirmed human deaths resulting from infection of H5N1 to the number of those confirmed cases of infection with the virus. For example, if there are 100 confirmed cases of a disease and 50 die as a consequence, then the CFR is 50%. The case fatality rate does not take into account cases of a disease which are unconfirmed or undiagnosed, perhaps because symptoms were mild and unremarkable or because of a lack of diagnostic facilities. The Infection Fatality Rate (IFR) is adjusted to allow for undiagnosed cases.

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

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.

<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.

AS03 is the trade name for a squalene-based immunologic adjuvant used in various vaccine products by GlaxoSmithKline (GSK). It is used, for example, in GSK's A/H1N1 pandemic flu vaccine Pandemrix. It is also in Arepanrix and the Q-pan for H5N1 influenza. A dose of AS03 adjuvant contains

<span class="mw-page-title-main">Universal flu vaccine</span> Vaccine that prevents infection from all strains of the flu

A universal flu vaccine would be a flu vaccine effective against all human -adapted strains of influenza A and influenza B regardless of the virus sub type, or any antigenic drift or antigenic shift. Hence it should not require modification from year to year in order to keep up with changes in the influenza virus. As of 2024 no universal flu vaccine had been successfully developed, however several candidate vaccines were in development, with some undergoing early stage clinical trial.

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.

References

  1. ↑ "Health product highlights 2021: Annexes of products approved in 2021". Health Canada . 3 August 2022. Retrieved 25 March 2024.
  2. 1 2 "Audenz". U.S. Food and Drug Administration (FDA). 31 January 2020. STN: 125692. Retrieved 5 February 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  3. ↑ Keown, Alex (4 February 2020). "FDA Approves Seqirus' Audenz as Vaccine Against Potential Flu Pandemic". BioSpace. Retrieved 5 February 2020.
  4. ↑ "H5N1 Influenza Virus Vaccine Questions and Answers". U.S. Food and Drug Administration (FDA). 17 April 2007. Retrieved 5 February 2020.
  5. ↑ "Diagnostic Targets and Potential Vaccine Against H5n1 Avian Influenza". U.S. Food and Drug Administration (FDA). 11 September 2019. Retrieved 5 February 2020.
  6. ↑ "EU licenses first pre-pandemic bird flu vaccine LONDON". Reuters. May 19, 2008.
  7. 1 2 "Adjupanrix EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 13 January 2021.
  8. 1 2 "Foclivia EPAR". European Medicines Agency . 17 September 2018. Retrieved 13 January 2021.
  9. 1 2 "Aflunov EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 13 January 2021.
  10. ↑ "Pumarix EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 13 January 2021.
  11. ↑ "Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted, manufactured". U.S. Food and Drug Administration (FDA). 22 November 2013. Retrieved 5 February 2020.
  12. ↑ "Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted". U.S. Food and Drug Administration (FDA). 23 April 2019. STN#: 125419. Retrieved 5 February 2020.
  13. ↑ Lowes, Roberts (22 November 2013). "FDA Approves First Adjuvanted Vaccine for H5N1 Bird Flu". Medscape. Retrieved 16 March 2015.
  14. ↑ "Commission secures access for Member States to 665,000 doses of zoonotic influenza vaccines to prevent avian flu". European Commission. 11 June 2024.
  15. ↑ According to the U.S. HHS (United States Department of Health & Human Services) Pandemic Influenza Plan Appendix F: Current HHS Activities last revised on November 8, 2005 at "United States Department of Health and Human Services". Archived from the original on 2007-02-14. Retrieved 2017-09-09.
  16. ↑ Bardiya N, Bae J (2005). "Influenza vaccines: recent advances in production technologies". Appl Microbiol Biotechnol. 67 (3): 299–305. doi:10.1007/s00253-004-1874-1. PMID   15660212. S2CID   25307879.
  17. ↑ Grady, Denise (March 30, 2006). "Doubt Cast on Stockpile of a Vaccine for Bird Flu". The New York Times .
  18. ↑ "Wired News". Archived from the original on 2006-06-28. Retrieved 2017-03-07.
  19. ↑ Gao W, Soloff AC, Lu X, Montecalvo A, Nguyen DC, Matsuoka Y, Robbins PD, Swayne DE, Donis RO, Katz JM, Barratt-Boyes SM, Gambotto A (February 2006). "Protection of mice and poultry from lethal H5N1 avian influenza virus through adenovirus-based immunization". J. Virol. 80 (4): 1959–64. doi: 10.1128/JVI.80.4.1959-1964.2006 . PMC   1367171 . PMID   16439551.
  20. ↑ Department of Health & Human Services Archived 2007-02-14 at the Wayback Machine
  21. ↑ NAID – 2004 News Archived 2010-03-08 at the Wayback Machine NAID – 2005 News Archived 2010-03-08 at the Wayback Machine
  22. ↑ "U.S. Plan to Stockpile Bird-Flu Vaccine a Big Gamble". NPR.org. 6 January 2006. Retrieved 6 February 2020.
  23. ↑ Treanor JJ, Campbell JD, Zangwill KM, Rowe T, Wolff M (March 2006). "Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine". N. Engl. J. Med. 354 (13): 1343–51. doi: 10.1056/NEJMoa055778 . PMID   16571878.
  24. ↑ Poland GA (March 2006). "Vaccines against avian influenza--a race against time". N. Engl. J. Med. 354 (13): 1411–3. doi: 10.1056/NEJMe068047 . PMID   16571885.
  25. ↑ "WHO changes H5N1 strains for pandemic vaccines, raising concern over virus evolution". CIDRAP. 18 August 2006. Retrieved 5 February 2020.
  26. ↑ WHO (PDF) Archived 2006-08-24 at the Wayback Machine article Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as pre-pandemic vaccines published August 18, 2006
  27. ↑ "HHS: Most H5N1 vaccine on hand is still potent". CIDRAP. 17 November 2006. Retrieved 5 February 2020.
  28. ↑ "IFPMA glossary". Archived from the original on 2006-05-23. Retrieved 2012-06-13.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.