How Broadly Neutralising Antibodies Are Redefining Immunity to Influenza

Overview

Journal Antibodies (Basel)

Date 2025 Jan 23

PMID 39846612

Authors

Rebecca Steventon

Lucas Stolle

Craig Peter Thompson

Affiliations

Soon will be listed here.

Abstract

Recent avian influenza outbreaks have heightened global concern over viral threats with the potential to significantly impact human health. Influenza is particularly alarming due to its history of causing pandemics and zoonotic reservoirs. In response, significant progress has been made toward the development of universal influenza vaccines, largely driven by the discovery of broadly neutralising antibodies (bnAbs), which have the potential to neutralise a broad range of influenza viruses, extending beyond the traditional strain-specific response. This could lead to longer-lasting immunity, reducing the need for seasonal vaccinations, and improve preparedness for future pandemics. This review offers a comprehensive analysis of these antibodies, their application in clinical studies, and both their potential and possible shortcomings in managing future influenza outbreaks.

References

Joyce M, Wheatley A, Thomas P, Chuang G, Soto C, Bailer R . Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses. Cell. 2016; 166(3):609-623. PMC: 4978566. DOI: 10.1016/j.cell.2016.06.043. View

GERHARD W, Yewdell J, Frankel M, Webster R . Antigenic structure of influenza virus haemagglutinin defined by hybridoma antibodies. Nature. 1981; 290(5808):713-7. DOI: 10.1038/290713a0. View

Yu X, Tsibane T, McGraw P, House F, Keefer C, Hicar M . Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature. 2008; 455(7212):532-6. PMC: 2848880. DOI: 10.1038/nature07231. View

Portnoff A, Patel N, Massare M, Zhou H, Tian J, Zhou B . Influenza Hemagglutinin Nanoparticle Vaccine Elicits Broadly Neutralizing Antibodies against Structurally Distinct Domains of H3N2 HA. Vaccines (Basel). 2020; 8(1). PMC: 7157642. DOI: 10.3390/vaccines8010099. View

Monsalvo A, Batalle J, Lopez M, Krause J, Klemenc J, Hernandez J . Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes. Nat Med. 2010; 17(2):195-9. PMC: 3034774. DOI: 10.1038/nm.2262. View

Limberis M, Adam V, Wong G, Gren J, Kobasa D, Ross T . Intranasal antibody gene transfer in mice and ferrets elicits broad protection against pandemic influenza. Sci Transl Med. 2013; 5(187):187ra72. PMC: 4596530. DOI: 10.1126/scitranslmed.3006299. View

McCarthy K, Watanabe A, Kuraoka M, Do K, McGee C, Sempowski G . Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires. Immunity. 2018; 48(1):174-184.e9. PMC: 5810956. DOI: 10.1016/j.immuni.2017.12.009. View

Wu Y, Cho M, Shore D, Song M, Choi J, Jiang T . A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus. Nat Commun. 2015; 6:7708. PMC: 4518248. DOI: 10.1038/ncomms8708. View

Guthmiller J, Han J, Li L, Freyn A, Liu S, Stovicek O . First exposure to the pandemic H1N1 virus induced broadly neutralizing antibodies targeting hemagglutinin head epitopes. Sci Transl Med. 2021; 13(596). PMC: 10173203. DOI: 10.1126/scitranslmed.abg4535. View

10.

Zuo Y, Wang P, Sun J, Guo S, Wang G, Zuo T . Complementary recognition of the receptor-binding site of highly pathogenic H5N1 influenza viruses by two human neutralizing antibodies. J Biol Chem. 2018; 293(42):16503-16517. PMC: 6200926. DOI: 10.1074/jbc.RA118.004604. View

11.

Ali S, Takas T, Nyborg A, Shoemaker K, Kallewaard N, Chiong R . Evaluation of MEDI8852, an Anti-Influenza A Monoclonal Antibody, in Treating Acute Uncomplicated Influenza. Antimicrob Agents Chemother. 2018; 62(11). PMC: 6201130. DOI: 10.1128/AAC.00694-18. View

12.

Kohler G, Milstein C . Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975; 256(5517):495-7. DOI: 10.1038/256495a0. View

13.

Lee P, Yoshida R, Ekiert D, Sakai N, Suzuki Y, Takada A . Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity. Proc Natl Acad Sci U S A. 2012; 109(42):17040-5. PMC: 3479480. DOI: 10.1073/pnas.1212371109. View

14.

Neerukonda S, Vassell R, Weiss C . Neutralizing Antibodies Targeting the Conserved Stem Region of Influenza Hemagglutinin. Vaccines (Basel). 2020; 8(3). PMC: 7563823. DOI: 10.3390/vaccines8030382. View

15.

Zheng Z, Paul S, Mo X, Yuan Y, Tan Y . The Vestigial Esterase Domain of Haemagglutinin of H5N1 Avian Influenza A Virus: Antigenicity and Contribution to Viral Pathogenesis. Vaccines (Basel). 2018; 6(3). PMC: 6161130. DOI: 10.3390/vaccines6030053. View

16.

Myers M, Gallagher J, Kim A, Payne W, Maldonado-Puga S, Assimakopoulos H . Commercial influenza vaccines vary in HA-complex structure and in induction of cross-reactive HA antibodies. Nat Commun. 2023; 14(1):1763. PMC: 10060936. DOI: 10.1038/s41467-023-37162-z. View

17.

Tan G, Lee P, Hoffman R, Mazel-Sanchez B, Krammer F, Leon P . Characterization of a broadly neutralizing monoclonal antibody that targets the fusion domain of group 2 influenza A virus hemagglutinin. J Virol. 2014; 88(23):13580-92. PMC: 4248980. DOI: 10.1128/JVI.02289-14. View

18.

Guthmiller J, Han J, Utset H, Li L, Lan L, Henry C . Broadly neutralizing antibodies target a haemagglutinin anchor epitope. Nature. 2021; 602(7896):314-320. PMC: 8828479. DOI: 10.1038/s41586-021-04356-8. View

19.

Iba Y, Fujii Y, Ohshima N, Sumida T, Kubota-Koketsu R, Ikeda M . Conserved neutralizing epitope at globular head of hemagglutinin in H3N2 influenza viruses. J Virol. 2014; 88(13):7130-44. PMC: 4054433. DOI: 10.1128/JVI.00420-14. View

20.

van der Lubbe J, Huizingh J, Verspuij J, Tettero L, Schmit-Tillemans S, Mooij P . Mini-hemagglutinin vaccination induces cross-reactive antibodies in pre-exposed NHP that protect mice against lethal influenza challenge. NPJ Vaccines. 2018; 3:25. PMC: 6030213. DOI: 10.1038/s41541-018-0063-7. View