Universal flu vaccine explained

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.[1] [2] [3] 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.[4] [5]

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.[6]

If a universal vaccine can be developed which is both effective and safe, it could be manufactured in quantity and eliminate availability and supply issues of current vaccines.[7]

Influenza virus

Human influenza is principally caused by the Influenza A and Influenza B viruses. Both have similar structure, being enveloped RNA virus. Their protein membrane contains the glycoproteins hemagglutinin (HA) and neuraminidase (NA) which are used by the virus to enter a host cell, and subsequently to release newly manufactured virions from the host cell. Each strain of the influenza virus has a different pattern of glycoproteins; the glycoproteins themselves have variability as well.[3] [8]

History

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.[9] 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.[10]

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.[11] [12]

By 2010 some universal flu vaccines had started clinical trials.

DNA vaccines, such as VGX-3400X (aimed at multiple H5N1 strains), contain DNA fragments (plasmids).[17] [18] Inovio's SynCon DNA vaccines include H5N1 and H1N1 subtypes.[19]

Other companies pursuing the vaccine as of 2009 and 2010 include Theraclone,[20] VaxInnate,[21] Crucell NV,[22] Inovio Pharmaceuticals, Immune Targeting Systems (ITS)[23] and iQur.[24]

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.[25]

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.[26]

Some people given a 2009 H1N1 flu vaccine have developed broadly protective antibodies, raising hopes for a universal flu vaccine.[27] [28] [29]

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.[30]

In July 2011, researchers created an antibody, which targets a protein found on the surface of all influenza A viruses called haemagglutinin.[31] [32] [33] 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. 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.[34]

Other vaccines are polypeptide based.[35]

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.[36]

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.[37]

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.[38]

There have been some clinical trials of the M-001[39] [40] [41] 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 PhaseIII 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.[42] [43]

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.[44] [45]

See also

Further reading

Notes and References

  1. . April 2017 . Universal influenza virus vaccines and therapeutic antibodies . . 23 . 4 . 222–228 . 10.1016/j.cmi.2017.02.009 . 5389886 . 28216325.
  2. Khanna M, Sharma S, Kumar B, Rajput R . 25 May 2014 . Protective Immunity Based on the Conserved Hemagglutinin Stalk Domain and Its Prospects for Universal Influenza Vaccine Development . . Review . 2014 . 546274 . 10.1155/2014/546274 . 2314-6133 . 4055638 . 24982895 . 546274 . free.
  3. Book: Sherwood, Linda M . Prescott's Microbiology . 10th . McGraw-Hill Education . 9781259281594 . 2017 .
  4. Web site: 2023-05-15 . Clinical trial of mRNA universal influenza vaccine candidate begins . 2024-06-14 . National Institutes of Health (NIH) . EN.
  5. Web site: 2023-09-15 . NIH clinical trial of universal flu vaccine candidate begins . 2024-06-14 . National Institutes of Health (NIH) . EN.
  6. Web site: Corona . Angel . vanc . 3 August 2020 . A Universal Influenza Vaccine: How Close Are We? . 3 June 2023 . American Society for Microbiology.
  7. Gottlieb . Tanya . Ben-Yedidia . Tamar . Epitope-based approaches to a universal influenza vaccine . Journal of Autoimmunity . November 2014 . 54 . 15–20 . 10.1016/j.jaut.2014.07.005 . 25172355 .
  8. Web site: CDC . 2023-03-30 . Types of Influenza Viruses . 2024-06-14 . Centers for Disease Control and Prevention . en-us.
  9. Web site: Universal Influenza Vaccine Tested Successfully In Humans . January 25, 2008 . ScienceDaily .
  10. The Wistar Institute obtains patent for universal flu vaccine technology . https://web.archive.org/web/20100110051048/http://www.wistar.org/news_info/pressreleases/pr_05.06.09.htm . January 10, 2010 . Wistar Institute .
  11. July 15, 2010 . NIH Scientists Advance Universal Flu Vaccine . NIH .
  12. 10.1126/science.1192517 . Induction of Broadly Neutralizing H1N1 Influenza Antibodies by Vaccination . 2010 . Wei . Chih-Jen . Boyington . Jeffrey C. . McTamney . Patrick M. . Kong . Wing-Pui . Pearce . Melissa B. . Xu . Ling . Andersen . Hanne . Rao . Srinivas . Tumpey . Terrence M. . Yang . Zhi-Yong . Nabel . Gary J. . Science . 329 . 5995 . 1060–1064 . 20647428 . 2010Sci...329.1060W . 44753716 .
  13. News: Shpurer . Sharon . Copaxone Inventor Ruth Arnon Taking BiondVax Public. Haaretz . 22 April 2007 . en.
  14. Dance . Amber . 30 March 2012 . News: Moving towards a universal flu vaccine. Nature. 10.1038/nature.2012.10333. 72653506.
  15. Web site: New Research May Lead to a Replacement for Annual Flu Shots KentConnects Blog Post . 2024-06-14 . www.kentscientific.com.
  16. News: Immune Targeting Systems – FP01 Influenza, undated page . its-innovation.com . https://web.archive.org/web/20150131165453/http://www.its-innovation.com/pipeline/fp01-influenza/ . January 31, 2015.
  17. News: Inovio Pharmaceuticals, Inc. Immunizes First Subject In U.S. Influenza DNA Vaccine Clinical Trial. https://archive.today/20130201070518/http://www.reuters.com/finance/stocks/keyDevelopments?rpc=66&symbol=INO&timestamp=20100615103000. dead. 2013-02-01. Reuters.
  18. Web site: Inovio Biomedical's SynCon preventive DNA vaccine receives approval in Korea for Phase I clinical trial. March 2, 2010. News-Medical.net.
  19. News: 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.
  20. http://seattletimes.nwsource.com/html/localnews/2012228358_flu29m.html Seattle's Theraclone makes a 'first step' on long road to universal flu vaccine
  21. http://www.fiercebiotech.com/press-releases/vaxinnates-universal-flu-vaccine-candidate-shown-safe-and-immunogenic-phase-i-clinica VaxInnate's Universal Flu Vaccine Candidate Shown Safe and Immunogenic in Phase I Clinical Study
  22. http://www.allbusiness.com/pharmaceuticals-biotechnology/pharmaceutical-agents/13070919-1.html Johnson & Johnson pursues vaccine firm
  23. http://www.its-innovation.com/about-us/ Immune Targeting Systems – About Us
  24. Web site: FLUTCORE Report Summary. European Commission. dead. https://web.archive.org/web/20170427003918/http://cordis.europa.eu/result/rcn/167831_en.html. 27 April 2017.
  25. Web site: Centivax Universal Influenza Vaccine Grand Challenges. gcgh.grandchallenges.org. 2020-01-28.
  26. Lambert LC, Fauci AS . Influenza vaccines for the future . The New England Journal of Medicine . 363 . 21 . 2036–44 . November 2010 . 21083388 . 10.1056/NEJMra1002842 . free .
  27. News: H1N1 Gives Clues to Universal Flu Vaccine. January 18, 2011. September 17, 2017. January 22, 2014. https://web.archive.org/web/20140122081319/http://www.pbs.org/newshour/updates/health/jan-june11/flu_01-18.html. dead.
  28. 6. Wrammert J, Koutsonanos D, Li GM, Edupuganti S, Sui J, Morrissey M, McCausland M, Skountzou I, Hornig M, Lipkin WI, Mehta A, Razavi B, Del Rio C, Zheng NY, Lee JH, Huang M, Ali Z, Kaur K, Andrews S, Amara RR, Wang Y, Das SR, O'Donnell CD, Yewdell JW, Subbarao K, Marasco WA, Mulligan MJ, Compans R, Ahmed R, Wilson PC. January 2011. 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. 10.1084/jem.20101352. 3023136. 21220454.
  29. News: A vaccine for all flu seasons. Spring 2011.
  30. Valkenburg . Sophie A. . Mallajosyula . V. Vamsee Aditya . Li . Olive T. W. . Chin . Alex W. H. . Carnell . George . Temperton . Nigel . Varadarajan . Raghavan . Poon . Leo L. M. . 2016 . Stalking influenza by vaccination with pre-fusion headless HA mini-stem . Scientific Reports . en . 6 . 1 . 22666 . 10.1038/srep22666 . 26947245 . 4780079 . 2016NatSR...622666V . 2045-2322.
  31. News: 'Super antibody' fights off flu . Gallagher . James . BBC News . 29 July 2011 .
  32. Web site: Scientists hail the prospect of a universal vaccine for flu. July 29, 2011. The Independent.
  33. http://www.huffingtonpost.com/2011/07/28/universal-flu-vaccine-antibody_n_912603.html "Universal Flu Vaccine On The Horizon: Researchers Find 'Super Antibody'"
  34. http://mbio.asm.org/content/1/1/e00018-10.abstract Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain
  35. Wang TT, Tan GS, Hai R, Pica N, Ngai L, Ekiert DC, Wilson IA, García-Sastre A, Moran TM, Palese P. November 2010. 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. 2010PNAS..10718979W. 10.1073/pnas.1013387107. 2973924. 20956293. free.
  36. Web site: The Second Annual Einstein-Montefiore Presidential Lecture: William R. Jacobs, Ph.D., Lecture (3of3). 10 May 2018 . www.youtube.com.
  37. 10.1126/science.aay0678 . Broadly protective human antibodies that target the active site of influenza virus neuraminidase . 2019 . Stadlbauer . Daniel . Zhu . Xueyong . McMahon . Meagan . Turner . Jackson S. . Wohlbold . Teddy J. . Schmitz . Aaron J. . Strohmeier . Shirin . Yu . Wenli . Nachbagauer . Raffael . Mudd . Philip A. . Wilson . Ian A. . Ellebedy . Ali H. . Krammer . Florian . Science . 366 . 6464 . 499–504 . 31649200 . 7105897 . 2019Sci...366..499S .
  38. Taylor A, "First Universal Flu Vaccine to Enter Phase 3 Trial" "The Scientist", 2018
  39. Atsmon J, Caraco Y, Ziv-Sefer S, Shaikevich D, Abramov E, Volokhov I, Bruzil S, Haima KY, Gottlieb T, Ben-Yedidia T . 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 . 25173483 . 10.1016/j.vaccine.2014.08.031 .
  40. van Doorn E, Liu H, Ben-Yedidia T, Hassin S, Visontai I, Norley S, Frijlink HW, Hak E . 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 . 28296763 . 5369918 . 10.1097/MD.0000000000006339 .
  41. Abbasi J . The Search for a Universal Flu Vaccine Heats Up . JAMA . 322. 20. November 2019 . 1942–1944 . 31693060 . 10.1001/jama.2019.16816 . 207903441 .
  42. Web site: Phillipson . Josh . BiondVax Announces Topline Results from Phase 3 Clinical Trial of the M-001 Universal Influenza Vaccine Candidate . BiondVax .
  43. Web site: NIH begins first-in-human trial of a universal influenza vaccine candidate . National Institutes of Health (NIH) . April 3, 2019 . https://web.archive.org/web/20191112194242/https://www.nih.gov/news-events/news-releases/nih-begins-first-human-trial-universal-influenza-vaccine-candidate . November 12, 2019 . live . November 12, 2019.
  44. Bernstein . David I . Guptill . Jeffrey . Naficy . Abdollah . Nachbagauer . Raffael . Berlanda-Scorza . Francesco . Feser . Jodi . Wilson . Patrick C . Solórzano . Alicia . Van der Wielen . Marie . Walter . Emmanuel B . Albrecht . Randy A . Buschle . Kristen N . Chen . Yao-qing . Claeys . Carine . Dickey . Michelle . Dugan . Haley L . Ermler . Megan E . Freeman . Debra . Gao . Min . Gast . Christopher . Guthmiller . Jenna J . Hai . Rong . Henry . Carole . Lan . Linda Yu-Ling . McNeal . Monica . Palm . Anna-Karin E . Shaw . Dustin G . Stamper . Christopher T . Sun . Weina . Sutton . Victoria . Tepora . Micah E . Wahid . Rahnuma . Wenzel . Heather . Wohlbold . Teddy John . Innis . Bruce L . García-Sastre . Adolfo . Palese . Peter . Krammer . Florian . 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 . January 2020 . 20 . 1 . 80–91 . 10.1016/S1473-3099(19)30393-7 . 31630990. 6928577 . free .
  45. Nachbagauer . Raffael . Feser . Jodi . Naficy . Abdollah . Bernstein . David I. . Guptill . Jeffrey . Walter . Emmanuel B. . Berlanda-Scorza . Franceso . Stadlbauer . Daniel . Wilson . Patrick C. . Aydillo . Teresa . Behzadi . Mohammad Amin . Bhavsar . Disha . Bliss . Carly . Capuano . Christina . Carreño . Juan Manuel . Chromikova . Veronika . Claeys . Carine . Coughlan . Lynda . Freyn . Alec W. . Gast . Christopher . Javier . Andres . Jiang . Kaijun . Mariottini . Chiara . McMahon . Meagan . McNeal . Monica . Solórzano . Alicia . Strohmeier . Shirin . Sun . Weina . Van der Wielen . Marie . Innis . Bruce L. . García-Sastre . Adolfo . Palese . Peter . Krammer . Florian . 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 . 7 December 2020 . 27 . 1 . 106–114 . 10.1038/s41591-020-1118-7. 33288923 . free .

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