Mini-hemagglutinin Vaccination Induces Cross-reactive Antibodies in Pre-exposed NHP That Protect Mice Against Lethal Influenza Challenge

Overview

Journal NPJ Vaccines

Date 2018 Jul 7

PMID 29977611

Citations 16

Authors

Joan E M van der Lubbe

Jeroen Huizingh

Johan W A Verspuij

Lisanne Tettero

Sonja P R Schmit-Tillemans

Petra Mooij

Daniella Mortier

Gerrit Koopman

Willy M J M Bogers

Liesbeth Dekking

Wim Meijberg

Ted Kwaks

Boerries Brandenburg

Jeroen T B M Tolboom

Hanneke Schuitemaker

Ramon Roozendaal

Harmjan Kuipers

Roland C Zahn

Affiliations

Soon will be listed here.

Abstract

Seasonal vaccines are currently the most effective countermeasure against influenza. However, seasonal vaccines are only effective against strains closely related to the influenza strains contained in the vaccine. Recently a new hemagglutinin (HA) stem-based antigen, the so-called "mini-HA", has been shown to induce a cross-protective immune response in influenza-naive mice and non-human primates (NHP). However, prior exposure to influenza can have a profound effect on the immune response to subsequent influenza infection and the protective efficacy of vaccination. Here we show that mini-HA, compared to a trivalent influenza vaccine (TIV), elicits a broadened influenza-specific humoral immune response in NHP previously exposed to influenza. Serum transfer experiments showed that antibodies induced by both mini-HA and seasonal vaccine protected mice against lethal challenge with a H1N1 influenza strain heterologous to the H1 HA included in the TIV. However, antibodies elicited by mini-HA showed an additional benefit of protecting mice against lethal heterosubtypic H5N1 influenza challenge, associated with H5 HA-specific functional antibodies.

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References

Cobey S, Hensley S . Immune history and influenza virus susceptibility. Curr Opin Virol. 2017; 22:105-111. PMC: 5467731. DOI: 10.1016/j.coviro.2016.12.004. View

Li G, Chiu C, Wrammert J, McCausland M, Andrews S, Zheng N . Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. Proc Natl Acad Sci U S A. 2012; 109(23):9047-52. PMC: 3384143. DOI: 10.1073/pnas.1118979109. View

Caton A, Brownlee G, Yewdell J, GERHARD W . The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell. 1982; 31(2 Pt 1):417-27. DOI: 10.1016/0092-8674(82)90135-0. View

Nachbagauer R, Choi A, Hirsh A, Margine I, Iida S, Barrera A . Defining the antibody cross-reactome directed against the influenza virus surface glycoproteins. Nat Immunol. 2017; 18(4):464-473. PMC: 5360498. DOI: 10.1038/ni.3684. View

Corti D, Suguitan Jr A, Pinna D, Silacci C, Fernandez-Rodriguez B, Vanzetta F . Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine. J Clin Invest. 2010; 120(5):1663-73. PMC: 2860935. DOI: 10.1172/JCI41902. View

Roozendaal R, Tolboom J, Roos A, Riahi S, Theeuwsen J, Bujny M . Transient humoral protection against H5N1 challenge after seasonal influenza vaccination of humans. PLoS One. 2014; 9(7):e103550. PMC: 4116209. DOI: 10.1371/journal.pone.0103550. View

Vatti A, Monsalve D, Pacheco Y, Chang C, Anaya J, Gershwin M . Original antigenic sin: A comprehensive review. J Autoimmun. 2017; 83:12-21. DOI: 10.1016/j.jaut.2017.04.008. View

DiLillo D, Palese P, Wilson P, Ravetch J . Broadly neutralizing anti-influenza antibodies require Fc receptor engagement for in vivo protection. J Clin Invest. 2016; 126(2):605-10. PMC: 4731186. DOI: 10.1172/JCI84428. View

Bodewes R, de Mutsert G, van der Klis F, Ventresca M, Wilks S, Smith D . Prevalence of antibodies against seasonal influenza A and B viruses in children in Netherlands. Clin Vaccine Immunol. 2011; 18(3):469-76. PMC: 3067385. DOI: 10.1128/CVI.00396-10. View

10.

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

11.

DiLillo D, Tan G, Palese P, Ravetch J . Broadly neutralizing hemagglutinin stalk-specific antibodies require FcγR interactions for protection against influenza virus in vivo. Nat Med. 2014; 20(2):143-51. PMC: 3966466. DOI: 10.1038/nm.3443. View

12.

Ellebedy A, Krammer F, Li G, Miller M, Chiu C, Wrammert J . Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans. Proc Natl Acad Sci U S A. 2014; 111(36):13133-8. PMC: 4246941. DOI: 10.1073/pnas.1414070111. View

13.

Bodewes R, Kreijtz J, Geelhoed-Mieras M, van Amerongen G, Verburgh R, van Trierum S . Vaccination against seasonal influenza A/H3N2 virus reduces the induction of heterosubtypic immunity against influenza A/H5N1 virus infection in ferrets. J Virol. 2011; 85(6):2695-702. PMC: 3067975. DOI: 10.1128/JVI.02371-10. View

14.

Wei C, Yassine H, McTamney P, Gall J, Whittle J, Boyington J . Elicitation of broadly neutralizing influenza antibodies in animals with previous influenza exposure. Sci Transl Med. 2012; 4(147):147ra114. DOI: 10.1126/scitranslmed.3004273. View

15.

Tricco A, Chit A, Soobiah C, Hallett D, Meier G, Chen M . Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis. BMC Med. 2013; 11:153. PMC: 3706345. DOI: 10.1186/1741-7015-11-153. View

16.

Bodewes R, Kreijtz J, Baas C, Geelhoed-Mieras M, de Mutsert G, van Amerongen G . Vaccination against human influenza A/H3N2 virus prevents the induction of heterosubtypic immunity against lethal infection with avian influenza A/H5N1 virus. PLoS One. 2009; 4(5):e5538. PMC: 2678248. DOI: 10.1371/journal.pone.0005538. View

17.

Jegaskanda S, Vanderven H, Wheatley A, Kent S . Fc or not Fc; that is the question: Antibody Fc-receptor interactions are key to universal influenza vaccine design. Hum Vaccin Immunother. 2017; 13(6):1-9. PMC: 5489290. DOI: 10.1080/21645515.2017.1290018. View

18.

Lin S, Liu W, Jan J, Wu S . Glycan masking of hemagglutinin for adenovirus vector and recombinant protein immunizations elicits broadly neutralizing antibodies against H5N1 avian influenza viruses. PLoS One. 2014; 9(3):e92822. PMC: 3966833. DOI: 10.1371/journal.pone.0092822. View

19.

Graves P, SCHULMAN J, Young J, Palese P . Preparation of influenza virus subviral particles lacking the HA1 subunit of hemagglutinin: unmasking of cross-reactive HA2 determinants. Virology. 1983; 126(1):106-16. DOI: 10.1016/0042-6822(83)90465-8. View

20.

Lin S, Lin Y, Chong P, Wu S . Broader neutralizing antibodies against H5N1 viruses using prime-boost immunization of hyperglycosylated hemagglutinin DNA and virus-like particles. PLoS One. 2012; 7(6):e39075. PMC: 3374787. DOI: 10.1371/journal.pone.0039075. View