Restrained expansion of the recall germinal center response as biomarker of protection for influenza vaccination in mice


Autoři: Laurens P. Kil aff001;  Joost Vaneman aff001;  Joan E. M. van der Lubbe aff001;  Dominika Czapska-Casey aff001;  Jeroen T. B. M. Tolboom aff001;  Ramon Roozendaal aff001;  Roland C. Zahn aff001;  Harmjan Kuipers aff001;  Laura Solforosi aff001
Působiště autorů: Janssen Vaccines & Prevention B.V., Pharmaceutical Companies of Johnson and Johnson, Leiden, The Netherlands aff001
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225063

Souhrn

Correlates of protection (CoP) are invaluable for iterative vaccine design studies, especially in pursuit of complex vaccines such as a universal influenza vaccine (UFV) where a single antigen is optimized to elicit broad protection against many viral antigenic variants. Since broadly protective antibodies against influenza virus often exhibit mutational evidence of prolonged diversification, we studied germinal center (GC) kinetics in hemagglutinin (HA) immunized mice. Here we report that as early as 4 days after secondary immunization, the expansion of HA-specific GC B cells inversely correlated to protection against influenza virus challenge, induced by the antigen. In contrast, follicular T helper (TFH) cells did not expand differently after boost vaccination, suggestive of a B-cell intrinsic difference in activation and differentiation inferred by protective antigen properties. Importantly, differences in antigen dose only affected GC B-cell frequencies after primary immunization. The absence of accompanying differences in total anti-HA or epitope-specific antibody levels induced by vaccines of different efficacy suggests that the GC B-cell response upon revaccination represents an early and unique marker of protection that may significantly accelerate the pre-clinical phase of vaccine development.

Klíčová slova:

Antibodies – Antibody response – B cells – Enzyme-linked immunoassays – Immune response – Vaccination and immunization – Vaccines – Antigen isotypes


Zdroje

1. Salk JE, Menke WJ Jr F T J. A clinical, epidemiological and immunological evaluation of vaccination against epidemic influenza. Am J Hyg. 1945;42:57–93.

2. Virelizier J-L. Host Defenses Against Influenza Virus: The Role of Anti-Hemagglutinin Antibody. J Immunol [Internet]. 1975 Aug 1;115(2):434 LP–439. Available from: http://www.jimmunol.org/content/115/2/434.abstract

3. Gerdil C. The annual production cycle for influenza vaccine. Vaccine. 2003;21(16):1776–9. doi: 10.1016/s0264-410x(03)00071-9 12686093

4. Tricco AC, Chit A, Soobiah C, Hallett D, Meier G, Chen MH, et al. Comparing influenza vaccine efficacy against mismatched and matched strains: A systematic review and meta-analysis. BMC Med [Internet]. 2013;11(1). Available from: http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L52650360%0Ahttp://www.biomedcentral.com/1741-7015/11/153%0Ahttp://dx.doi.org/10.1186/1741-7015-11-153

5. Krammer F, Palese P. Advances in the development of influenza virus vaccines. Nat Rev Drug Discov [Internet]. 2015 Feb 27;14:167. Available from: http://dx.doi.org/10.1038/nrd4529 25722244

6. Paules CI, Sullivan SG, Subbarao K, Fauci AS. Chasing Seasonal Influenza—The Need for a Universal Influenza Vaccine. N Engl J Med [Internet]. 2017 Nov 29;378(1):7–9. Available from: http://dx.doi.org/10.1056/NEJMp1714916 29185857

7. Yassine HM, Boyington JC, McTamney PM, Wei CJ, Kanekiyo M, Kong WP, et al. Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat Med. 2015;21(9):1065–70. doi: 10.1038/nm.3927 26301691

8. Paules CI, Marston HD, Eisinger RW, Baltimore D, Fauci AS. The Pathway to a Universal Influenza Vaccine. Immunity [Internet]. 2017;47(4):599–603. Available from: https://doi.org/10.1016/j.immuni.2017.09.007 29045889

9. Ohmit SE, Petrie JG, Cross RT, Johnson E, Monto AS. Influenza hemagglutination-inhibition antibody titer as a correlate of vaccine-induced protection. J Infect Dis. 2011;204(12):1879–85. doi: 10.1093/infdis/jir661 21998477

10. Brandenburg B, Koudstaal W, Goudsmit J, Klaren V, Tang C, Bujny M V, et al. Mechanisms of Hemagglutinin Targeted Influenza Virus Neutralization. PLoS One [Internet]. 2013 Dec 11;8(12):e80034. Available from: https://doi.org/10.1371/journal.pone.0080034 24348996

11. Hannoun C, Megas F, Piercy J. Immunogenicity and protective efficacy of influenza vaccination. Virus Res [Internet]. 2004 Jul 1 [cited 2019 Feb 3];103(1–2):133–8. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0168170204001248?via%3Dihub doi: 10.1016/j.virusres.2004.02.025 15163501

12. van der Lubbe JEM, Verspuij JWA, Huizingh J, Schmit-Tillemans SPR, Tolboom JTBM, Dekking LEHA, et al. Mini-HA Is Superior to Full Length Hemagglutinin Immunization in Inducing Stem-Specific Antibodies and Protection Against Group 1 Influenza Virus Challenges in Mice. Front Immunol [Internet]. 2018;9(October):1–13. Available from: https://www.frontiersin.org/article/10.3389/fimmu.2018.02350/full

13. Impagliazzo A, Milder F, Kuipers H, Wagner M V., Zhu X, Hoffman RMB, et al. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science (80-). 2015;349(6254):1301–6.

14. Cho A, Wrammert J. Implications of broadly neutralizing antibodies in the development of a universal influenza vaccine. Curr Opin Virol [Internet]. 2016;17:110–5. Available from: http://dx.doi.org/10.1016/j.coviro.2016.03.002 27031684

15. Victora GD, Wilson PC. Germinal Center Selection and the Antibody Response to Influenza. Cell [Internet]. 2015;163(3):545–8. Available from: http://dx.doi.org/10.1016/j.cell.2015.10.004 26496601

16. Lingwood D, McTamney PM, Yassine HM, Whittle JRR, Guo X, Boyington JC, et al. Structural and genetic basis for development of broadly neutralizing influenza antibodies. Nature [Internet]. 2012;489(7417):566–70. Available from: http://dx.doi.org/10.1038/nature11371 22932267

17. Pappas L, Foglierini M, Piccoli L, Kallewaard NL, Turrini F, Silacci C, et al. Rapid development of broadly influenza neutralizing antibodies through redundant mutations. Nature [Internet]. 2014;516(7531):418–22. Available from: http://dx.doi.org/10.1038/nature13764 25296253

18. Ellebedy AH, Krammer F, Li G-M, Miller MS, Chiu C, Wrammert J, et al. Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans. Proc Natl Acad Sci [Internet]. 2014;111(36):13133–8. Available from: http://www.pnas.org/cgi/doi/10.1073/pnas.1414070111 25157133

19. Andrews SF, Huang Y, Kaur K, Popova LI, Ho IY, Pauli NT, et al. Immune history profoundly affects broadly protective B cell responses to influenza. Sci Transl Med. 2015;7(316).

20. Henry C, Palm AKE, Krammer F, Wilson PC. From Original Antigenic Sin to the Universal Influenza Virus Vaccine. Trends Immunol [Internet]. 2018;39(1):70–9. Available from: http://dx.doi.org/10.1016/j.it.2017.08.003 28867526

21. Adachi Y, Onodera T, Yamada Y, Daio R, Tsuiji M, Inoue T, et al. Distinct germinal center selection at local sites shapes memory B cell response to viral escape. J Exp Med [Internet]. 2015;212(10):1709–23. Available from: http://www.jem.org/lookup/doi/10.1084/jem.20142284 26324444

22. Keating R, Hertz T, Wehenkel M, Harris TL, Edwards BA, McClaren JL, et al. The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus. Nat Immunol [Internet]. 2013;14(12):1266–76. Available from: http://dx.doi.org/10.1038/ni.2741 24141387

23. Popp MW, Antos JM, Grotenbreg GM, Spooner E, Ploegh HL. Sortagging: A versatile method for protein labeling. Nat Chem Biol. 2007;3(11):707–8. doi: 10.1038/nchembio.2007.31 17891153

24. Tomayko MM, Steinel NC, Anderson SM, Shlomchik MJ. Cutting Edge: Hierarchy of Maturity of Murine Memory B Cell Subsets. J Immunol [Internet]. 2010;185(12):7146–50. Available from: http://www.jimmunol.org/cgi/doi/10.4049/jimmunol.1002163 21078902

25. Weisel FJ, Zuccarino-Catania G V., Chikina M, Shlomchik MJ. A Temporal Switch in the Germinal Center Determines Differential Output of Memory B and Plasma Cells. Immunity [Internet]. 2016;44(1):116–30. Available from: http://dx.doi.org/10.1016/j.immuni.2015.12.004 26795247

26. Amanna IJ, Slifka MK. Quantitation of rare memory B cell populations by two independent and complementary approaches. J Immunol Methods. 2006;317(1–2):175–85. doi: 10.1016/j.jim.2006.09.005 17055526

27. Tan H-X, Kent SJ, Wheatley AK. Subdominance and poor intrinsic immunogenicity limit humoral immunity targeting influenza HA stem The Journal of Clinical Investigation. J Clin Invest [Internet]. 2019;129(2):850–62. Available from: https://dm5migu4zj3pb.cloudfront.net/manuscripts/123000/123366/cache/123366.3-20190131154233-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf doi: 10.1172/JCI123366 30521496

28. Nair N, Buti L, Faenzi E, Buricchi F, Nuti S, Sammicheli C, et al. Optimized fluorescent labeling to identify memory B cells specific for Neisseria meningitidis serogroup B vaccine antigens ex vivo. Immunity, Inflamm Dis [Internet]. 2013;1(1):3–13. Available from: http://doi.wiley.com/10.1002/iid3.3

29. Schmidt AG, Therkelsen MD, Stewart S, Kepler TB, Liao HX, Moody MA, et al. Viral receptor-binding site antibodies with diverse germline origins. Cell [Internet]. 2015;161(5):1026–34. Available from: http://dx.doi.org/10.1016/j.cell.2015.04.028 25959776

30. Dreyfus C, Laursen NS, Kwaks T, Zuijdgeest D, Khayat R, Ekiert DC, et al. Highly conserved protective epitopes on influenza B viruses. Science (80-). 2012;337(6100):1343–8.

31. Baumjohann D, Preite S, Reboldi A, Ronchi F, Ansel KM, Lanzavecchia A, et al. Persistent Antigen and Germinal Center B Cells Sustain T Follicular Helper Cell Responses and Phenotype. Immunity [Internet]. 2013;38(3):596–605. Available from: http://dx.doi.org/10.1016/j.immuni.2012.11.020 23499493

32. Maamary J, Wang TT, Tan GS, Palese P, Ravetch J V. Increasing the breadth and potency of response to the seasonal influenza virus vaccine by immune complex immunization. Proc Natl Acad Sci [Internet]. 2017;114(38):201707950. Available from: http://www.pnas.org/lookup/doi/10.1073/pnas.1707950114

33. Wang TT, Maamary J, Tan GS, Bournazos S, Davis CW, Krammer F, et al. Anti-HA Glycoforms Drive B Cell Affinity Selection and Determine Influenza Vaccine Efficacy. Cell [Internet]. 2015;162(1):160–9. Available from: http://dx.doi.org/10.1016/j.cell.2015.06.026 26140596

34. Paus D, Phan TG, Chan TD, Gardam S, Basten A, Brink R. Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation. J Exp Med [Internet]. 2006;203(4):1081–91. Available from: http://www.jem.org/lookup/doi/10.1084/jem.20060087 16606676

35. Fagarasan S, Muramatsu M, Suzuki K, Nagaoka H, Hiai H, Honjo T. Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora. Science (80-). 2002;298(5597):1424–7.

36. Havenar-Daughton C, Lindqvist M, Heit A, Wu JE, Reiss SM, Kendric K, et al. CXCL13 is a plasma biomarker of germinal center activity. Proc Natl Acad Sci [Internet]. 2016;113(10):2702–7. Available from: http://www.pnas.org/lookup/doi/10.1073/pnas.1520112113 26908875

37. Koutsakos M, Wheatley AK, Loh L, Clemens EB, Sant S, Nüssing S, et al. Circulating TFHcells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity. Sci Transl Med. 2018;10(428):1–16.

38. Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G, et al. Human Blood CXCR5+CD4+T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion. Immunity [Internet]. 2011;34(1):108–21. Available from: http://dx.doi.org/10.1016/j.immuni.2010.12.012 21215658


Článek vyšel v časopise

PLOS One


2019 Číslo 11