Universal flu vaccine

A universal flu vaccine is flu vaccine that is effective against all influenza virus strains regardless of the virus subtype or viral genetic drift.[1] Hence it should not require modification from year to year. As of 2017, there was no approved universal flu vaccine for general use, but several have been in development.[1]

Development predictions

On February 13, 2013, U.S. Food and Drug Administration (FDA) Chief Scientist Jesse Goodman predicted that a universal flu vaccine was still at least 5 to 10 years away. When asked about the prospects of a universal flu vaccine in a hearing before House Energy and Commerce Subcommittee on Oversight and Investigations, Goodman replied "Nature is very tricky and as this is a very crafty virus, so I'd be very hesitant to predict... I think the earliest we'd begin to see something with clinical benefit might be 5 to 10 years."[2]

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-vecto-based vaccine.[3]

The NIAID/NIH state that "developing new and improved vaccines is a high priority".[4] The BIO2016 convention featured a panel discussion titled "Solving the Flu Problem: Can New Technologies Lead to Universal Flu Vaccines?"[5] featuring speakers from BARDA and industry.

Research

Some people given a 2009 H1N1 flu vaccine have developed broadly protective antibodies, raising hopes for a universal flu vaccine.[6][7][8]

A 'vaccine'/antigen 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.[9]

In July 2011, researchers created an antibody, which targets a protein found on the surface of all influenza A viruses called haemagglutinin.[10][11][12] F16 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.[10][11][12] 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.[13]

Other vaccines are polypeptide based.[14]

A recent 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 1st, 2018 the same vaccine can be used in a modified way to contain hemagglutinin and invoke a special ADCC immune response.[15]

Clinical development

DNA vaccines, such as VGX-3400X (aimed at multiple H5N1 strains), contain DNA fragments (plasmids).[16][17] Inovio's SynCon DNA vaccines include H5N1 and H1N1 subtypes.[18]

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.[19] See also H5N1 vaccines.

In 2009, the Wistar Institute received a patent for using "a variety of peptides" in a flu vaccine, and announced it was seeking a corporate partner.[20]

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 virus.[21]

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[22][23]
  • ITS's fp01[24] includes 6 peptide antigens to highly conserved segments of the PA, PB1, PB2, NP & M1 proteins, and has started phase I trials.

Other companies pursuing the vaccine as of 2009 and 2010 include Theraclone,[25] VaxInnate,[26] Crucell NV,[27] Inovio Pharmaceuticals,[16] Immune Targeting Systems (ITS)[28] and iQur.[29]

References

  1. 1 2 Nachbagauer R, Krammer F (April 2017). "Universal influenza virus vaccines and therapeutic antibodies". Clinical Microbiology and Infection. 23 (4): 222–228. doi:10.1016/j.cmi.2017.02.009. PMID 28216325.
  2. ↑ Roos R. "FDA expert: Universal flu vaccine still 5–10 years off". Center for Infectious Disease Research and Policy (CIDRAP). Retrieved Feb 13, 2013.
  3. ↑ Lambert LC, Fauci AS (November 2010). "Influenza vaccines for the future". The New England Journal of Medicine. 363 (21): 2036–44. doi:10.1056/NEJMra1002842. PMID 21083388.
  4. ↑ "Flu (Influenza) Vaccine Research". www.niaid.nih.gov. Retrieved 2016-06-30.
  5. ↑ "myBIO 2016 - Session/Event Details". mybio.org. Retrieved 2016-06-30.
  6. ↑ "H1N1 Gives Clues to Universal Flu Vaccine". January 18, 2011.
  7. ↑ Wrammert J, Koutsonanos D, Li GM, Edupuganti S, Sui J, Morrissey M, et al. (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. doi:10.1084/jem.20101352. PMC 3023136. PMID 21220454.
  8. ↑ "A vaccine for all flu seasons". Spring 2011.
  9. ↑ Stalking influenza by vaccination with pre-fusion headless HA mini-stem. 2016
  10. 1 2 BBC: 'Super antibody' fights off flu
  11. 1 2 Independent: Scientists hail the prospect of a universal vaccine for flu
  12. 1 2 "Universal Flu Vaccine On The Horizon: Researchers Find 'Super Antibody'" The Huffington Post. July 28, 2011
  13. ↑ Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain
  14. ↑ 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. Bibcode:2010PNAS..10718979W. doi:10.1073/pnas.1013387107. PMC 2973924. PMID 20956293.
  15. ↑ JacobsJr: 'The Second Annual Einstein-Montefiore Presidential Lecture: William R. Jacobs, Ph.D., Lecture'
  16. 1 2 "Inovio Pharmaceuticals, Inc. Immunizes First Subject In U.S. Influenza DNA Vaccine Clinical Trial". Reuters.
  17. ↑ Inovio Biomedical's SynCon preventive DNA vaccine receives approval in Korea for Phase I clinical trial
  18. ↑ "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.
  19. ↑ "Universal Influenza Vaccine Tested Successfully In Humans".
  20. ↑ The Wistar Institute obtains patent for universal flu vaccine technology Archived January 10, 2010, at the Wayback Machine.. Wistar Institute.
  21. ↑ NIH Scientists Advance Universal Flu Vaccine. NIH.
  22. ↑ Shpurer, Sharon (22 April 2007). "Copaxone Inventor Ruth Arnon Taking BiondVax Public". Haaretz.
  23. ↑ Dance, Amber (30 March 2012). "News: Moving towards a universal flu vaccine". Nature. doi:10.1038/nature.2012.10333.
  24. ↑ Immune Targeting Systems – FP01 Influenza, undated page Archived January 31, 2015, at the Wayback Machine.
  25. ↑ Seattle's Theraclone makes a 'first step' on long road to universal flu vaccine Archived November 16, 2011, at the Wayback Machine.. The Seattle Times.
  26. ↑ VaxInnate's Universal Flu Vaccine Candidate Shown Safe and Immunogenic in Phase I Clinical Study. Fierce Biotech.
  27. ↑ Johnson & Johnson pursues vaccine firm. Charleston Gazette.
  28. ↑ Immune Targeting Systems – About Us Archived January 27, 2015, at the Wayback Machine.
  29. ↑ "FLUTCORE Report Summary". European Commission. Archived from the original on 27 April 2017.

Further reading

  • Sautto GA, Kirchenbaum GA, Ross TM (January 2018). "Towards a universal influenza vaccine: different approaches for one goal". Virology Journal. 15 (1): 17. doi:10.1186/s12985-017-0918-y. PMID 29370862.
  • Sano K, Ainai A, Suzuki T, Hasegawa H (September 2017). "The road to a more effective influenza vaccine: Up to date studies and future prospects". Vaccine. 35 (40): 5388–5395. doi:10.1016/j.vaccine.2017.08.034. PMID 28866292.
  • Krammer F (May 2017). "Strategies to induce broadly protective antibody responses to viral glycoproteins". Expert Review of Vaccines. 16 (5): 503–513. doi:10.1080/14760584.2017.1299576. PMID 28277797.
  • Stadlbauer D, Nachbagauer R, Meade P, Krammer F (December 2017). "Universal influenza virus vaccines: what can we learn from the human immune response following exposure to H7 subtype viruses?". Frontiers of Medicine. 11 (4): 471–479. doi:10.1007/s11684-017-0602-z. PMID 29159597.
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