Challenges of Making Effective Influenza Vaccines

Overview

Journal Annu Rev Virol

Publisher Annual Reviews

Specialty Microbiology

Date 2020 May 12

PMID 32392457

Citations 23

Authors

Sigrid Gouma

Elizabeth M Anderson

Scott E Hensley

Affiliations

Soon will be listed here.

Abstract

Seasonal influenza vaccines prevent influenza-related illnesses, hospitalizations, and deaths. However, these vaccines are not as effective as other viral vaccines, and there is clearly room for improvement. Here, we review the history of seasonal influenza vaccines, describe challenges associated with producing influenza vaccine antigens, and discuss the inherent difficulties of updating influenza vaccine strains each influenza season. We argue that seasonal influenza vaccines can be dramatically improved by modernizing antigen production processes and developing models that are better at predicting viral evolution. Resources should be specifically dedicated to improving seasonal influenza vaccines while developing entirely new vaccine platforms.

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References

Lin Y, Wharton S, Whittaker L, Dai M, Ermetal B, Lo J . The characteristics and antigenic properties of recently emerged subclade 3C.3a and 3C.2a human influenza A(H3N2) viruses passaged in MDCK cells. Influenza Other Respir Viruses. 2017; 11(3):263-274. PMC: 5410720. DOI: 10.1111/irv.12447. View

Cowling B, Perera R, Valkenburg S, Leung N, Iuliano A, Tam Y . Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial. Clin Infect Dis. 2019; 71(7):1704-1714. PMC: 7289658. DOI: 10.1093/cid/ciz1034. View

Neher R, Russell C, Shraiman B . Predicting evolution from the shape of genealogical trees. Elife. 2014; 3. PMC: 4227306. DOI: 10.7554/eLife.03568. View

Erbelding E, Post D, Stemmy E, Roberts P, Augustine A, Ferguson S . A Universal Influenza Vaccine: The Strategic Plan for the National Institute of Allergy and Infectious Diseases. J Infect Dis. 2018; 218(3):347-354. PMC: 6279170. DOI: 10.1093/infdis/jiy103. View

DiazGranados C, Dunning A, Kimmel M, Kirby D, Treanor J, Collins A . Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014; 371(7):635-45. DOI: 10.1056/NEJMoa1315727. View

Sanyal M, Holmes T, Maecker H, Albrecht R, Dekker C, He X . Diminished B-Cell Response After Repeat Influenza Vaccination. J Infect Dis. 2018; 219(10):1586-1595. PMC: 6473172. DOI: 10.1093/infdis/jiy685. View

Morris D, Gostic K, Pompei S, Bedford T, Luksza M, Neher R . Predictive Modeling of Influenza Shows the Promise of Applied Evolutionary Biology. Trends Microbiol. 2017; 26(2):102-118. PMC: 5830126. DOI: 10.1016/j.tim.2017.09.004. View

Francis T, MAGILL T . THE ANTIBODY RESPONSE OF HUMAN SUBJECTS VACCINATED WITH THE VIRUS OF HUMAN INFLUENZA. J Exp Med. 2009; 65(2):251-9. PMC: 2133482. DOI: 10.1084/jem.65.2.251. View

Dunkle L, Izikson R, Patriarca P, Goldenthal K, Muse D, Callahan J . Efficacy of Recombinant Influenza Vaccine in Adults 50 Years of Age or Older. N Engl J Med. 2017; 376(25):2427-2436. DOI: 10.1056/NEJMoa1608862. View

10.

Pebody R, McMenamin J, Nohynek H . Live attenuated influenza vaccine (LAIV): recent effectiveness results from the USA and implications for LAIV programmes elsewhere. Arch Dis Child. 2017; 103(1):101-105. DOI: 10.1136/archdischild-2016-312165. View

11.

Valesano A, Fitzsimmons W, McCrone J, Petrie J, Monto A, Martin E . Influenza B Viruses Exhibit Lower Within-Host Diversity than Influenza A Viruses in Human Hosts. J Virol. 2019; 94(5). PMC: 7022338. DOI: 10.1128/JVI.01710-19. View

12.

HIRST G . THE QUANTITATIVE DETERMINATION OF INFLUENZA VIRUS AND ANTIBODIES BY MEANS OF RED CELL AGGLUTINATION. J Exp Med. 2009; 75(1):49-64. PMC: 2135212. DOI: 10.1084/jem.75.1.49. View

13.

Rogers G, Paulson J . Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology. 1983; 127(2):361-73. DOI: 10.1016/0042-6822(83)90150-2. View

14.

Garretson T, Petrie J, Martin E, Monto A, Hensley S . Identification of human vaccinees that possess antibodies targeting the egg-adapted hemagglutinin receptor binding site of an H1N1 influenza vaccine strain. Vaccine. 2018; 36(28):4095-4101. PMC: 5995672. DOI: 10.1016/j.vaccine.2018.05.086. View

15.

Khurana S, Hahn M, Coyle E, King L, Lin T, Treanor J . Repeat vaccination reduces antibody affinity maturation across different influenza vaccine platforms in humans. Nat Commun. 2019; 10(1):3338. PMC: 6659679. DOI: 10.1038/s41467-019-11296-5. View

16.

Schild G, Wood J, Newman R . A single-radial-immunodiffusion technique for the assay of influenza haemagglutinin antigen. Proposals for an assay method for the haemagglutinin content of influenza vaccines. Bull World Health Organ. 1975; 52(2):223-31. PMC: 2366365. View

17.

KILBOURNE E, Johansson B, Grajower B . Independent and disparate evolution in nature of influenza A virus hemagglutinin and neuraminidase glycoproteins. Proc Natl Acad Sci U S A. 1990; 87(2):786-90. PMC: 53351. DOI: 10.1073/pnas.87.2.786. View

18.

KILBOURNE E . Future influenza vaccines and the use of genetic recombinants. Bull World Health Organ. 1969; 41(3):643-5. PMC: 2427719. View

19.

Skowronski D, Sabaiduc S, Leir S, Rose C, Zou M, Murti M . Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV). Euro Surveill. 2019; 24(46). PMC: 6864978. DOI: 10.2807/1560-7917.ES.2019.24.46.1900585. View

20.

Russell C, Jones T, Barr I, Cox N, Garten R, Gregory V . The global circulation of seasonal influenza A (H3N2) viruses. Science. 2008; 320(5874):340-6. DOI: 10.1126/science.1154137. View