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HandWiki. Universal Flu Vaccine. Encyclopedia. Available online: https://encyclopedia.pub/entry/31597 (accessed on 20 April 2024).
HandWiki. Universal Flu Vaccine. Encyclopedia. Available at: https://encyclopedia.pub/entry/31597. Accessed April 20, 2024.
HandWiki. "Universal Flu Vaccine" Encyclopedia, https://encyclopedia.pub/entry/31597 (accessed April 20, 2024).
HandWiki. (2022, October 27). Universal Flu Vaccine. In Encyclopedia. https://encyclopedia.pub/entry/31597
HandWiki. "Universal Flu Vaccine." Encyclopedia. Web. 27 October, 2022.
Universal Flu Vaccine
Edit

A universal flu vaccine is a flu vaccine that is effective against all influenza strains regardless of the virus sub type, antigenic drift or antigenic shift. Hence it should not require modification from year to year. As of 2021 no universal flu vaccine had been approved for general use, several were in development, and one was in clinical trial.

universal flu vaccine flu vaccine antigenic drift

1. Medical Uses

New vaccines against currently circulating influenza variants are required every year due to the diversity of flu viruses and variable efficacy of vaccines to prevent them. A universal vaccine would eliminate the need to create a vaccine for each year's variants. The efficacy of a vaccine refers to the protection against a broad variety of influenza strains. Events such as antigenic shift have created pandemic strains such as the H1N1 outbreak in 2009. The research required every year to isolate a potential popular viral strain and create a vaccine to defend against it is a six-month-long process; during that time the virus can mutate, making the vaccines less effective.[1]

High-risk populations, including the elderly and those with chronic disease, often acquire only limited immunity towards the flu from vaccines. The vaccines have been found to be 30% to 70% effective in preventing hospitalization from the flu or pneumonia.

On average influenza vaccine efficacy is 60% among the general population that receive yearly vaccinations.

A universal vaccine could be manufactured in quantity and eliminate availability and supply issues of current vaccines.[2] There is conflicting evidence on whether it would cut costs.[3]

2. Structure of Influenza

Influenza A is involved in most strains of the flu. It is an enveloped RNA virus. It has a protein membrane containing the glycoproteins hemagglutinin (HA) and neuraminidase (NA) which are used by the virus to enter a host cell and to release itself and its copies from the host cell. Each strain of the influenza virus has a different pattern of glycoproteins; the glycoproteins themselves have variability as well.[4]

3. History

A prototype for a universal flu vaccine. The blue protein scaffold supports eight green influenza hemagglutinin proteins arrayed to present antibody binding sites

In 2008, Acambis announced work on a universal flu vaccine (ACAM-FLU-ATM) based on the less variable M2 protein component of the flu virus shell.[5] See also H5N1 vaccines.

In 2009, the Wistar Institute in Pennsylvania received a patent for using "a variety of peptides" in a flu vaccine, and announced it was seeking a corporate partner.[6]

In 2010, the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. NIH announced a breakthrough; the effort targets the stem, which mutates less often than the head of the viral HA.[7]

By 2010 some universal flu vaccines had started clinical trials.

  • BiondVax identified 9 conserved epitopes of the influenza virus and combined them into a recombinant protein called Multimeric-001.[8][9] All seven of Biondvax's completed phase 2 human trials demonstrated safety and significant levels of immunogenicity. More recently, Biondvax (NASDAQ:BVXV) undertook a two-year, more than 12,400 participant phase 3 study of Multimeric-001, its candidate universal influenza vaccine. In October 2020, results of the phase 3 study were published, indicating no apparent efficacy.
  • ITS's fp01[10] includes 6 peptide antigens to highly conserved segments of the PA, PB1, PB2, NP & M1 proteins, and has started phase I trials.

DNA vaccines, such as VGX-3400X (aimed at multiple H5N1 strains), contain DNA fragments (plasmids).[11][12] Inovio's SynCon DNA vaccines include H5N1 and H1N1 subtypes.[13]

Other companies pursuing the vaccine as of 2009 and 2010 include Theraclone,[14] VaxInnate,[15] Crucell NV,[16] Inovio Pharmaceuticals,[11] Immune Targeting Systems (ITS)[17] and iQur.[18]

In 2019, Distributed Bio completed pre-clinical trials of a vaccine that consists of computationally selected distant evolutionary variants of hemagglutinin epitopes and is expected to begin human trials in 2021.[19]

In recent years, research has concerned use of an antigen for the flu hemagglutinin (HA) stem. Based on the results of animal studies, a universal flu vaccine may use a two-step vaccination strategy: priming with a DNA-based HA vaccine, followed by a second dose with an inactivated, attenuated, or adenovirus-vector-based vaccine.[20]

Some people given a 2009 H1N1 flu vaccine have developed broadly protective antibodies, raising hopes for a universal flu vaccine.[21][22][23]

A vaccine based on the hemagglutinin (HA) stem was the first to induce "broadly neutralizing" antibodies to both HA-group 1 and HA-group 2 influenza in mice.[24]

In July 2011, researchers created an antibody, which targets a protein found on the surface of all influenza A viruses called haemagglutinin.[25] [26][27] FI6 is the only known antibody that binds (its neutralizing activity is controversial) to all 16 subtypes of the influenza A virus hemagglutinin and might be the lynchpin for a universal influenza vaccine.[25][26][27] The subdomain of the hemagglutinin that is targeted by FI6, namely the stalk domain, was actually successfully used earlier as universal influenza virus vaccine by Peter Palese's research group at Mount Sinai School of Medicine.[28]

Other vaccines are polypeptide based.[29]

4. Research

A study from the Albert Einstein College of Medicine, where researchers deleted gD-2 from the herpes virus, which is responsible for HSV microbes entering in and out of cells showed as of May 1, 2018 the same vaccine can be used in a modified way to contain hemagglutinin and invoke a special ADCC immune response.[30]

The Washington University School of Medicine in St.Louis and the Icahn School of Medicine in Mount Sinai in New York are using the glycoprotein neuraminidase as a targeted antigen in their research. Three monoclonal antibodies (mAB) were sampled from a patient infected with influenza A H3N2 virus. The antibodies were able to bind to the neuraminidase active site neutralizing the virus across multiple strains. The site remains the same with minimal variability across most of the flu strains. In trials using mice all three antibodies were effective across multiple strains, one antibody was able to protect the mice from all 12 strains tested including human and non-human flu viruses. All mice used in the experiments survived even if the antibody was not administered until 72 hours after the time of infection.[31]

Simultaneously the NIAID is working on a peptide vaccine that is starting human clinical trials in the 2019 flu season. The study will include 10,000 participants who will be monitored for two flu seasons. The vaccine will show efficacy if it is able to reduce the number of influenza cases in all strains.[32]

There have been some clinical trials of the M-001[33][34][35][36][37] and H1ssF_3928 universal influenza vaccine candidates. As of August 2020, all seven M-001 trials are completed. Each one of these studies resulted in the conclusion that M-001 is safe, tolerable, and immunogenic. Their pivotal Phase III study with 12,400 participants was completed and results of the data analysis were published in October 2020, indicating that the vaccine did not show any statistical difference from the placebo group in reduction of flu illness and severity.[38][39][40]

In 2019–2020, a vaccine candidate from Peter Palese's group at Mount Sinai Hospital emerged from a phase 1 clinical trial with positive results. By vaccinating twice with hemagglutinins that have different "heads" but the same membrane-proximal "stalk", the immune system is directed to focus its attention on the conserved stalk.[41][42]

References

  1. Corona A. "A Universal Influenza Vaccine: How Close Are we?" "American Society for Microbiology", 2019 https://www.asm.org/Articles/2019/August/A-Universal-Influenza-Vaccine-How-Close-Are-We
  2. Gottlieb, Tanya; Ben-Yedidia, Tamar (2014). "Epitope-based approaches to a universal influenza vaccine". Journal of Autoimmunity (Elsevier BV) 54: 15–20. doi:10.1016/j.jaut.2014.07.005. ISSN 0896-8411. PMID 25172355. https://www.sciencedirect.com/science/article/pii/S0896841114001188. 
  3. France, Glenson; Wateska, Angela R; Nowalk, Mary Patricia; DePasse, Jay; Raviotta, Jonathan M; Shim, Eunha; Zimmerman, Richard K; Smith, Kenneth J (1 September 2018). "Potential Cost-Effectiveness of a Universal Influenza Vaccine in Older Adults". Innovation in Aging (Oxford University Press (OUP)) 2 (3): igy035. doi:10.1093/geroni/igy035. ISSN 2399-5300. PMID 30569023.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6293081
  4. Sherwood Linda M, Prescott's Microbiology (10th ed.) McGraw-Hill Education , 2017
  5. "Universal Influenza Vaccine Tested Successfully In Humans". https://www.sciencedaily.com/releases/2008/01/080124185522.htm. 
  6. The Wistar Institute obtains patent for universal flu vaccine technology . Wistar Institute. http://www.wistar.org/news_info/pressreleases/pr_05.06.09.htm
  7. NIH Scientists Advance Universal Flu Vaccine. NIH. http://www.nih.gov/news/health/jul2010/niaid-15.htm
  8. Shpurer, Sharon (22 April 2007). "Copaxone Inventor Ruth Arnon Taking BiondVax Public" (in en). Haaretz. https://www.haaretz.com/1.4817199. 
  9. Dance, Amber (30 March 2012). "News: Moving towards a universal flu vaccine". Nature. doi:10.1038/nature.2012.10333.  https://dx.doi.org/10.1038%2Fnature.2012.10333
  10. Immune Targeting Systems – FP01 Influenza, undated page http://www.its-innovation.com/pipeline/fp01-influenza/
  11. "Inovio Pharmaceuticals, Inc. Immunizes First Subject In U.S. Influenza DNA Vaccine Clinical Trial". Reuters. https://www.reuters.com/finance/stocks/keyDevelopments?rpc=66&symbol=INO×tamp=20100615103000. 
  12. "Inovio Biomedical's SynCon preventive DNA vaccine receives approval in Korea for Phase I clinical trial". March 2, 2010. https://www.news-medical.net/news/20100302/Inovio-Biomedicals-SynCon-preventive-DNA-vaccine-receives-approval-in-Korea-for-Phase-I-clinical-trial.aspx. 
  13. "Scientific Paper on Inovio Pharmaceuticals SynCon(TM) DNA Vaccines and Intradermal DNA Delivery Technology One of Most Cited Articles in the Journal Vaccine". October 14, 2010. http://www.marketwatch.com/story/scientific-paper-on-inovio-pharmaceuticals-syncontm-dna-vaccines-and-intradermal-dna-delivery-technology-one-of-most-cited-articles-in-the-journal-vaccine-2010-10-14?reflink=MW_news_stmp. 
  14. Seattle's Theraclone makes a 'first step' on long road to universal flu vaccine . The Seattle Times. http://seattletimes.nwsource.com/html/localnews/2012228358_flu29m.html
  15. VaxInnate's Universal Flu Vaccine Candidate Shown Safe and Immunogenic in Phase I Clinical Study. Fierce Biotech. http://www.fiercebiotech.com/press-releases/vaxinnates-universal-flu-vaccine-candidate-shown-safe-and-immunogenic-phase-i-clinica
  16. Johnson & Johnson pursues vaccine firm. Charleston Gazette. http://www.allbusiness.com/pharmaceuticals-biotechnology/pharmaceutical-agents/13070919-1.html
  17. Immune Targeting Systems – About Us http://www.its-innovation.com/about-us/
  18. "FLUTCORE Report Summary". European Commission. http://cordis.europa.eu/result/rcn/167831_en.html. 
  19. "Centivax Universal Influenza Vaccine | Grand Challenges". https://gcgh.grandchallenges.org/grant/centivax-universal-influenza-vaccine. 
  20. "Influenza vaccines for the future". The New England Journal of Medicine 363 (21): 2036–44. November 2010. doi:10.1056/NEJMra1002842. PMID 21083388.  https://dx.doi.org/10.1056%2FNEJMra1002842
  21. "H1N1 Gives Clues to Universal Flu Vaccine". January 18, 2011. https://www.pbs.org/newshour/updates/health/jan-june11/flu_01-18.html. 
  22. "Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection". The Journal of Experimental Medicine 208 (1): 181–93. January 2011. doi:10.1084/jem.20101352. PMID 21220454.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3023136
  23. "A vaccine for all flu seasons". Spring 2011. http://whsc.emory.edu/home/publications/health-sciences/emory-health/spring11/a-vaccine-for-all.html. 
  24. Stalking influenza by vaccination with pre-fusion headless HA mini-stem. 2016 http://www.nature.com/articles/srep22666
  25. Gallagher, James (29 July 2011). "'Super antibody' fights off flu". https://www.bbc.co.uk/news/health-14324901. 
  26. "Scientists hail the prospect of a universal vaccine for flu". July 29, 2011. http://www.independent.co.uk/news/science/scientists-hail-the-prospect-of-a-universal-vaccine-for-flu-2327993.html. 
  27. "Universal Flu Vaccine On The Horizon: Researchers Find 'Super Antibody'" The Huffington Post. July 28, 2011 http://www.huffingtonpost.com/2011/07/28/universal-flu-vaccine-antibody_n_912603.html
  28. Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain http://mbio.asm.org/content/1/1/e00018-10.abstract
  29. "Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes". Proceedings of the National Academy of Sciences of the United States of America 107 (44): 18979–84. November 2010. doi:10.1073/pnas.1013387107. PMID 20956293. Bibcode: 2010PNAS..10718979W.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2973924
  30. "The Second Annual Einstein-Montefiore Presidential Lecture: William R. Jacobs, Ph.D., Lecture (3of3)". https://www.youtube.com/watch?v=sBsUUW3UrSw. 
  31. Stadlbauer D, "Broadly protective human antibodies that target the active site of influenza virus neuraminidase" "Science", 2019 https://www.science.org/doi/10.1126/science.aay0678
  32. Taylor A, "First Universal Flu Vaccine to Enter Phase 3 Trial" "The Scientist", 2018 https://www.the-scientist.com/news-opinion/first-universal-flu-vaccine-to-enter-phase-3-trial-65073
  33. "Priming by a novel universal influenza vaccine (Multimeric-001)-a gateway for improving immune response in the elderly population". Vaccine 32 (44): 5816–23. October 2014. doi:10.1016/j.vaccine.2014.08.031. PMID 25173483.  https://dx.doi.org/10.1016%2Fj.vaccine.2014.08.031
  34. "Evaluating the immunogenicity and safety of a BiondVax-developed universal influenza vaccine (Multimeric-001) either as a standalone vaccine or as a primer to H5N1 influenza vaccine: Phase IIb study protocol". Medicine (Baltimore) 96 (11): e6339. March 2017. doi:10.1097/MD.0000000000006339. PMID 28296763.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5369918
  35. "The Search for a Universal Flu Vaccine Heats Up". JAMA 322 (20): 1942–1944. November 2019. doi:10.1001/jama.2019.16816. PMID 31693060.  https://dx.doi.org/10.1001%2Fjama.2019.16816
  36. Clinical trial number NCT03058692 for "Two Doses of Multimeric-001 (M-001) Followed by Influenza Vaccine" at ClinicalTrials.gov https://www.clinicaltrials.gov/show/NCT03058692
  37. Clinical trial number NCT03450915 for "A Pivotal Trial to Assess the Safety and Clinical Efficacy of the M-001 as a Standalone Universal Flu Vaccine" at ClinicalTrials.gov https://www.clinicaltrials.gov/show/NCT03450915
  38. Phillipson, Josh. "BiondVax Announces Topline Results from Phase 3 Clinical Trial of the M-001 Universal Influenza Vaccine Candidate". BiondVax. http://www.biondvax.com/2020/10/biondvax-announces-topline-results-from-phase-3-clinical-trial-of-the-m-001-universal-influenza-vaccine-candidate/. 
  39. "NIH begins first-in-human trial of a universal influenza vaccine candidate". April 3, 2019. https://www.nih.gov/news-events/news-releases/nih-begins-first-human-trial-universal-influenza-vaccine-candidate. 
  40. Clinical trial number NCT03814720 for "Dose, Safety, Tolerability and Immunogenicity of an Influenza H1 Stabilized Stem Ferritin Vaccine, VRCFLUNPF099-00-VP, in Healthy Adults" at ClinicalTrials.gov https://www.clinicaltrials.gov/show/NCT03814720
  41. Bernstein, David I; Guptill, Jeffrey; Naficy, Abdollah; Nachbagauer, Raffael; Berlanda-Scorza, Francesco; Feser, Jodi; Wilson, Patrick C; Solórzano, Alicia et al. (January 2020). "Immunogenicity of chimeric haemagglutinin-based, universal influenza virus vaccine candidates: interim results of a randomised, placebo-controlled, phase 1 clinical trial". The Lancet Infectious Diseases 20 (1): 80–91. doi:10.1016/S1473-3099(19)30393-7. PMID 31630990.  http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=6928577
  42. Nachbagauer, Raffael; Feser, Jodi; Naficy, Abdollah; Bernstein, David I.; Guptill, Jeffrey; Walter, Emmanuel B.; Berlanda-Scorza, Franceso; Stadlbauer, Daniel et al. (7 December 2020). "A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial". Nature Medicine 27 (1): 106–114. doi:10.1038/s41591-020-1118-7. PMID 33288923.  https://dx.doi.org/10.1038%2Fs41591-020-1118-7
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