Seasonal Influenza Vaccines: Variability of Immune Responses to B Lineage Viruses

Overview

Journal Hum Vaccin Immunother

Specialty Allergy & Immunology

Date 2024 Nov 18

PMID 39552079

Authors

Matthew S Miller

Emanuele Montomoli

Eyal Leshem

Michael Schotsaert

Thomas Weinke

Nevena Vicic

Deborah Rudin

Affiliations

Soon will be listed here.

Abstract

Although influenza A viruses predominate globally, influenza B viruses are responsible for a significant and often underappreciated burden. Despite this, immunity to influenza B viruses remains understudied, and there is a perception that vaccine-mediated immune responses to influenza B strains are less robust than influenza A strains. This targeted literature review examines this concept using data from pivotal phase 3 immunogenicity studies on currently licensed seasonal influenza vaccines and explores several explanations for this phenomenon, including immune exposure history, assay limitations, virus-related properties inherent to B lineages, and strain mismatch. Overall, studies demonstrated vaccines induce variable and sometimes less robust immune responses to influenza B strains; however, further studies are needed to fully confirm and understand these observations. In identifying the potential causes of variable performance of current vaccines against influenza, this review aims to guide vaccine development to enhance overall vaccine performance and reduce disease burden worldwide.

References

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

Zacour M, Ward B, Brewer A, Tang P, Boivin G, Li Y . Standardization of Hemagglutination Inhibition Assay for Influenza Serology Allows for High Reproducibility between Laboratories. Clin Vaccine Immunol. 2016; 23(3):236-42. PMC: 4783428. DOI: 10.1128/CVI.00613-15. View

Jones-Gray E, Robinson E, Kucharski A, Fox A, Sullivan S . Does repeated influenza vaccination attenuate effectiveness? A systematic review and meta-analysis. Lancet Respir Med. 2022; 11(1):27-44. PMC: 9780123. DOI: 10.1016/S2213-2600(22)00266-1. View

Koutsakos M, Illing P, Nguyen T, Mifsud N, Crawford J, Rizzetto S . Human CD8 T cell cross-reactivity across influenza A, B and C viruses. Nat Immunol. 2019; 20(5):613-625. DOI: 10.1038/s41590-019-0320-6. View

Matias G, Taylor R, Haguinet F, Schuck-Paim C, Lustig R, Fleming D . Modelling estimates of age-specific influenza-related hospitalisation and mortality in the United Kingdom. BMC Public Health. 2016; 16:481. PMC: 4898386. DOI: 10.1186/s12889-016-3128-4. View

Do T, Wheatley A, Kent S, Koutsakos M . Influenza B virus neuraminidase: a potential target for next-generation vaccines?. Expert Rev Vaccines. 2023; 23(1):39-48. DOI: 10.1080/14760584.2023.2290691. View

Neher R, Bedford T, Daniels R, Russell C, Shraiman B . Prediction, dynamics, and visualization of antigenic phenotypes of seasonal influenza viruses. Proc Natl Acad Sci U S A. 2016; 113(12):E1701-9. PMC: 4812706. DOI: 10.1073/pnas.1525578113. 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

Kirkpatrick E, Qiu X, Wilson P, Bahl J, Krammer F . The influenza virus hemagglutinin head evolves faster than the stalk domain. Sci Rep. 2018; 8(1):10432. PMC: 6041311. DOI: 10.1038/s41598-018-28706-1. View

10.

Miller M, Gardner T, Krammer F, Aguado L, Tortorella D, Basler C . Neutralizing antibodies against previously encountered influenza virus strains increase over time: a longitudinal analysis. Sci Transl Med. 2013; 5(198):198ra107. PMC: 4091683. DOI: 10.1126/scitranslmed.3006637. View

11.

Liu F, Gross F, Joshi S, Gaglani M, Naleway A, Murthy K . Redirecting antibody responses from egg-adapted epitopes following repeat vaccination with recombinant or cell culture-based versus egg-based influenza vaccines. Nat Commun. 2024; 15(1):254. PMC: 10767121. DOI: 10.1038/s41467-023-44551-x. View

12.

Skowronski D, Hottes T, De Serres G, Ward B, Janjua N, Sabaiduc S . Influenza Β/Victoria antigen induces strong recall of Β/Yamagata but lower Β/Victoria response in children primed with two doses of Β/Yamagata. Pediatr Infect Dis J. 2011; 30(10):833-9. DOI: 10.1097/INF.0b013e31822db4dc. View

13.

Zhong S, Ng T, Skowronski D, Iuliano A, Leung N, Perera R . Influenza A(H3N2) Antibody Responses to Standard-Dose Versus Enhanced Influenza Vaccine Immunogenicity in Older Adults and Prior Season's Vaccine Status. J Infect Dis. 2023; 229(5):1451-1459. PMC: 11095559. DOI: 10.1093/infdis/jiad497. View

14.

Belongia E, Simpson M, King J, Sundaram M, Kelley N, Osterholm M . Variable influenza vaccine effectiveness by subtype: a systematic review and meta-analysis of test-negative design studies. Lancet Infect Dis. 2016; 16(8):942-51. DOI: 10.1016/S1473-3099(16)00129-8. View

15.

Velkov T . The specificity of the influenza B virus hemagglutinin receptor binding pocket: what does it bind to?. J Mol Recognit. 2013; 26(10):439-49. DOI: 10.1002/jmr.2293. View

16.

Hartvickson R, Cruz M, Ervin J, Brandon D, Forleo-Neto E, Dagnew A . Non-inferiority of mammalian cell-derived quadrivalent subunit influenza virus vaccines compared to trivalent subunit influenza virus vaccines in healthy children: a phase III randomized, multicenter, double-blind clinical trial. Int J Infect Dis. 2015; 41:65-72. DOI: 10.1016/j.ijid.2015.11.004. View

17.

Madsen A, Dai Y, McMahon M, Schmitz A, Turner J, Tan J . Human Antibodies Targeting Influenza B Virus Neuraminidase Active Site Are Broadly Protective. Immunity. 2020; 53(4):852-863.e7. PMC: 7572813. DOI: 10.1016/j.immuni.2020.08.015. View

18.

Ward B, Pillet S, Charland N, Trepanier S, Couillard J, Landry N . The establishment of surrogates and correlates of protection: Useful tools for the licensure of effective influenza vaccines?. Hum Vaccin Immunother. 2017; 14(3):647-656. PMC: 5861778. DOI: 10.1080/21645515.2017.1413518. View

19.

Mosterin Hopping A, McElhaney J, Fonville J, Powers D, Beyer W, Smith D . The confounded effects of age and exposure history in response to influenza vaccination. Vaccine. 2015; 34(4):540-546. PMC: 4724805. DOI: 10.1016/j.vaccine.2015.11.058. View

20.

Skowronski D, Chambers C, De Serres G, Sabaiduc S, Winter A, Dickinson J . Age-Related Differences in Influenza B Infection by Lineage in a Community-Based Sentinel System, 2010-2011 to 2015-2016, Canada. J Infect Dis. 2017; 216(6):697-702. PMC: 5853978. DOI: 10.1093/infdis/jix393. View