1887

Abstract

mAbs constitute an important biological tool for influenza virus haemagglutinin (HA) epitope mapping through the generation of escape mutants, which could provide insights into immune evasion mechanisms and may benefit the future development of vaccines. Several influenza A (H1N1) pandemic 2009 (pdm09) HA escape mutants have been recently described. However, the HA antigenic sites of the previous seasonal A/Brisbane/59/2007 (H1N1) (Bris07) virus remain poorly documented. Here, we produced mAbs against pdm09 and Bris07 HA proteins expressed in human HEK293 cells. Escape mutants were generated using mAbs that exhibited HA inhibition and neutralizing activities. The resulting epitope mapping of the pdm09 HA protein revealed 11 escape mutations including three that were previously described (G172E, N173D and K256E) and eight novel ones (T89R, F128L, G157E, K180E, A212E, R269K, N311T and G478E). Among the six HA mutations that were part of predicted antigenic sites (Ca1, Ca2, Cb, Sa or Sb), three (G172E, N173D and K180E) were within the Sa site. Eight escape mutations (H54N, N55D, N55K, L60H, N203D, A231T, V314I and K464E) were obtained for Bris07 HA, and all but one (N203D, Sb site) were outside the predicted antigenic sites. Our results suggest that the Sa antigenic site is immunodominant in pdm09 HA, whereas the N203D mutation (Sb site), present in three different Bris07 escape mutants, appears as the immunodominant epitope in that strain. The fact that some mutations were not part of predicted antigenic sites reinforces the necessity of further characterizing the HA of additional H1N1 strains.

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2014-11-01
2019-11-18
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References

  1. Abed Y., Pizzorno A., Hamelin M. E., Leung A., Joubert P., Couture C., Kobasa D., Boivin G.. ( 2011;). The 2009 pandemic H1N1 D222G hemagglutinin mutation alters receptor specificity and increases virulence in mice but not in ferrets. . J Infect Dis 204:, 1008–1016. [CrossRef][PubMed]
    [Google Scholar]
  2. Abed Y., Pizzorno A., Bouhy X., Rhéaume C., Boivin G.. ( 2014;). Impact of potential permissive neuraminidase mutations on viral fitness of the H275Y oseltamivir-resistant influenza A(H1N1)pdm09 virus in vitro, in mice and in ferrets. . J Virol 88:, 1652–1658. [CrossRef][PubMed]
    [Google Scholar]
  3. Arora D. J., Tremblay P., Bourgault R., Boileau S.. ( 1985;). Concentration and purification of influenza virus from allantoic fluid. . Anal Biochem 144:, 189–192. [CrossRef][PubMed]
    [Google Scholar]
  4. Benjamin E., Wang W., McAuliffe J. M., Palmer-Hill F. J., Kallewaard N. L., Chen Z., Suzich J. A., Blair W. S., Jin H., Zhu Q.. ( 2014;). A broadly neutralizing human monoclonal antibody directed against a novel conserved epitope on the influenza virus H3 hemagglutinin globular head. . J Virol 88:, 6743–6750. [CrossRef][PubMed]
    [Google Scholar]
  5. Brownlee G. G., Fodor E.. ( 2001;). The predicted antigenicity of the haemagglutinin of the 1918 Spanish influenza pandemic suggests an avian origin. . Philos Trans R Soc Lond B Biol Sci 356:, 1871–1876. [CrossRef][PubMed]
    [Google Scholar]
  6. Caton A. J., Brownlee G. G., Yewdell J. W., Gerhard W.. ( 1982;). The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). . Cell 31:, 417–427. [CrossRef][PubMed]
    [Google Scholar]
  7. Centers for Disease Control and Prevention (CDC) ( 2009;). Outbreak of swine-origin influenza A (H1N1) virus infection – Mexico, March-April 2009. . MMWR Morb Mortal Wkly Rep 58:, 467–470.[PubMed]
    [Google Scholar]
  8. Chen J., Yan B., Chen Q., Yao Y., Wang H., Liu Q., Zhang S., Wang H., Chen Z.. ( 2014;). Evaluation of neutralizing efficacy of monoclonal antibodies specific for 2009 pandemic H1N1 influenza A virus in vitro and in vivo. . Arch Virol 159:, 471–483. [CrossRef][PubMed]
    [Google Scholar]
  9. Cutler J., Schleihauf E., Hatchette T. F., Billard B., Watson-Creed G., Davidson R., Li Y., Bastien N., Sarwal S..Nova Scotia Human Swine Influenza Investigation Team ( 2009;). Investigation of the first cases of human-to-human infection with the new swine-origin influenza A (H1N1) virus in Canada. . CMAJ 181:, 159–163. [CrossRef][PubMed]
    [Google Scholar]
  10. Deem M. W., Pan K.. ( 2009;). The epitope regions of H1-subtype influenza A, with application to vaccine efficacy. . Protein Eng Des Sel 22:, 543–546. [CrossRef][PubMed]
    [Google Scholar]
  11. Domingo E., Holland J. J.. ( 1997;). RNA virus mutations and fitness for survival. . Annu Rev Microbiol 51:, 151–178. [CrossRef][PubMed]
    [Google Scholar]
  12. Fraser C., Donnelly C. A., Cauchemez S., Hanage W. P., Van Kerkhove M. D., Hollingsworth T. D., Griffin J., Baggaley R. F., Jenkins H. E.. & other authors ( 2009;). Pandemic potential of a strain of influenza A (H1N1): early findings. . Science 324:, 1557–1561. [CrossRef][PubMed]
    [Google Scholar]
  13. Gerhard W., Yewdell J., Frankel M. E., Webster R.. ( 1981;). Antigenic structure of influenza virus haemagglutinin defined by hybridoma antibodies. . Nature 290:, 713–717. [CrossRef][PubMed]
    [Google Scholar]
  14. Hancock K., Veguilla V., Lu X., Zhong W., Butler E. N., Sun H., Liu F., Dong L., DeVos J. R.. & other authors ( 2009;). Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. . N Engl J Med 361:, 1945–1952. [CrossRef][PubMed]
    [Google Scholar]
  15. Hart G. W.. ( 1997;). Dynamic O-linked glycosylation of nuclear and cytoskeletal proteins. . Annu Rev Biochem 66:, 315–335. [CrossRef][PubMed]
    [Google Scholar]
  16. Hatakeyama S., Sakai-Tagawa Y., Kiso M., Goto H., Kawakami C., Mitamura K., Sugaya N., Suzuki Y., Kawaoka Y.. ( 2005;). Enhanced expression of an alpha2,6-linked sialic acid on MDCK cells improves isolation of human influenza viruses and evaluation of their sensitivity to a neuraminidase inhibitor. . J Clin Microbiol 43:, 4139–4146. [CrossRef][PubMed]
    [Google Scholar]
  17. Hausmann J., Kretzschmar E., Garten W., Klenk H. D.. ( 1997;). Biosynthesis, intracellular transport and enzymatic activity of an avian influenza A virus neuraminidase: role of unpaired cysteines and individual oligosaccharides. . J Gen Virol 78:, 3233–3245.[PubMed]
    [Google Scholar]
  18. Holder B. P., Simon P., Liao L. E., Abed Y., Bouhy X., Beauchemin C. A., Boivin G.. ( 2011;). Assessing the in vitro fitness of an oseltamivir-resistant seasonal A/H1N1 influenza strain using a mathematical model. . PLoS ONE 6:, e14767. [CrossRef][PubMed]
    [Google Scholar]
  19. Igarashi M., Ito K., Yoshida R., Tomabechi D., Kida H., Takada A.. ( 2010;). Predicting the antigenic structure of the pandemic (H1N1) 2009 influenza virus hemagglutinin. . PLoS ONE 5:, e8553. [CrossRef][PubMed]
    [Google Scholar]
  20. Köhler G., Milstein C.. ( 1975;). Continuous cultures of fused cells secreting antibody of predefined specificity. . Nature 256:, 495–497. [CrossRef][PubMed]
    [Google Scholar]
  21. Laemmli U. K.. ( 1970;). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. . Nature 227:, 680–685. [CrossRef][PubMed]
    [Google Scholar]
  22. Latterich M., Corbeil J.. ( 2008;). Label-free detection of biomolecular interactions in real time with a nano-porous silicon-based detection method. . Proteome Sci 6:, 31. [CrossRef][PubMed]
    [Google Scholar]
  23. Laver W. G., Webster R. G.. ( 1976;). Preparation and immunogenicity of an influenza virus hemagglutinin and neuraminidase subunit vaccine. . Virology 69:, 511–522. [CrossRef][PubMed]
    [Google Scholar]
  24. Lee M. S., Chen J. S.. ( 2004;). Predicting antigenic variants of influenza A/H3N2 viruses. . Emerg Infect Dis 10:, 1385–1390. [CrossRef][PubMed]
    [Google Scholar]
  25. Lubeck M. D., Gerhard W.. ( 1981;). Topological mapping antigenic sites on the influenza A/PR/8/34 virus hemagglutinin using monoclonal antibodies. . Virology 113:, 64–72. [CrossRef][PubMed]
    [Google Scholar]
  26. Malarchuk S., Irvin J.. ( 2010;). Antibody Screening and Characterization by Nanopore Optical Interferometry. San Diego, CA:: Silicon Kinetics Inc;. http://wwwsiliconkineticscom/pdf/SKI_Antibody_Screening_and_Characterization_Poster_2010pdf
    [Google Scholar]
  27. O’Donnell C. D., Vogel L., Wright A., Das S. R., Wrammert J., Li G. M., McCausland M., Zheng N. Y., Yewdell J. W.. & other authors ( 2012;). Antibody pressure by a human monoclonal antibody targeting the 2009 pandemic H1N1 virus hemagglutinin drives the emergence of a virus with increased virulence in mice. . MBio 3:, e00120–e12.[PubMed]
    [Google Scholar]
  28. Reid A. H., Fanning T. G., Janczewski T. A., Taubenberger J. K.. ( 2000;). Characterization of the 1918 “Spanish” influenza virus neuraminidase gene. . Proc Natl Acad Sci U S A 97:, 6785–6790. [CrossRef][PubMed]
    [Google Scholar]
  29. Robertson J. S., Engelhardt O. G.. ( 2010;). Developing vaccines to combat pandemic influenza. . Viruses 2:, 532–546. [CrossRef][PubMed]
    [Google Scholar]
  30. Robertson J. S., Nicolson C., Major D., Robertson E. W., Wood J. M.. ( 1993;). The role of amniotic passage in the egg-adaptation of human influenza virus is revealed by haemagglutinin sequence analyses. . J Gen Virol 74:, 2047–2051. [CrossRef][PubMed]
    [Google Scholar]
  31. Robertson J. S., Cook P., Attwell A. M., Williams S. P.. ( 1995;). Replicative advantage in tissue culture of egg-adapted influenza virus over tissue-culture derived virus: implications for vaccine manufacture. . Vaccine 13:, 1583–1588. [CrossRef][PubMed]
    [Google Scholar]
  32. Rudneva I., Ignatieva A., Timofeeva T., Shilov A., Kushch A., Masalova O., Klimova R., Bovin N., Mochalova L., Kaverin N.. ( 2012;). Escape mutants of pandemic influenza A/H1N1 2009 virus: variations in antigenic specificity and receptor affinity of the hemagglutinin. . Virus Res 166:, 61–67. [CrossRef][PubMed]
    [Google Scholar]
  33. Sanchez A. B., Nguyen T., Dema-Ala R., Kummel A. C., Kipps T. J., Messmer B. T.. ( 2010;). A general process for the development of peptide-based immunoassays for monoclonal antibodies. . Cancer Chemother Pharmacol 66:, 919–925. [CrossRef][PubMed]
    [Google Scholar]
  34. Skowronski D. M., Hamelin M. E., De Serres G., Janjua N. Z., Li G., Sabaiduc S., Bouhy X., Couture C., Leung A.. & other authors ( 2014;). Randomized controlled ferret study to assess the direct impact of 2008-09 trivalent inactivated influenza vaccine on A(H1N1)pdm09 disease risk. . PLoS ONE 9:, e86555. [CrossRef][PubMed]
    [Google Scholar]
  35. Stahl-Hennig C., Voss G., Nick S., Petry H., Fuchs D., Helmut W., Coulibaly C., Lüke W., Hunsmann G.. ( 1992;). Immunization with tween-ether-treated SIV adsorbed onto aluminum hydroxide protects monkeys against experimental SIV infection. . Virology 186:, 588–596. [CrossRef][PubMed]
    [Google Scholar]
  36. Steitz J., Barlow P. G., Hossain J., Kim E., Okada K., Kenniston T., Rea S., Donis R. O., Gambotto A.. ( 2010;). A candidate H1N1 pandemic influenza vaccine elicits protective immunity in mice. . PLoS ONE 5:, e10492. [CrossRef][PubMed]
    [Google Scholar]
  37. Stephan M., Kramer C., Steinem C., Janshoff A.. ( 2014;). Binding assay for low molecular weight analytes based on reflectometry of absorbing molecules in porous substrates. . Analyst (Lond) 139:, 1987–1992. [CrossRef][PubMed]
    [Google Scholar]
  38. Thoennes S., Li Z. N., Lee B. J., Langley W. A., Skehel J. J., Russell R. J., Steinhauer D. A.. ( 2008;). Analysis of residues near the fusion peptide in the influenza hemagglutinin structure for roles in triggering membrane fusion. . Virology 370:, 403–414. [CrossRef][PubMed]
    [Google Scholar]
  39. Towbin H., Staehelin T., Gordon J.. ( 1992;). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. 1979. . Biotechnology 24:, 145–149.[PubMed]
    [Google Scholar]
  40. Webster R. G., Hinshaw V. S., Laver W. G.. ( 1982;). Selection and analysis of antigenic variants of the neuraminidase of N2 influenza viruses with monoclonal antibodies. . Virology 117:, 93–104. [CrossRef][PubMed]
    [Google Scholar]
  41. WHO ( 2002;). Manual on animal influenza diagnosis and surveillance. . http://whqlibdocwhoint/hq/2002/who_cds_csr_ncs_20025pdf
  42. Wood J. M., Williams M. S.. ( 1998;). History of inactivated vaccines. . In Textbook of Influenza, , 2nd edn., pp. 317–323. Edited by Nicholson K. G., Webster R. G., Hay A. J... Oxford:: Blackwell Science;.
    [Google Scholar]
  43. Wu Y., Wu Y., Tefsen B., Shi Y., Gao G. F.. ( 2014;). Bat-derived influenza-like viruses H17N10 and H18N11. . Trends Microbiol 22:, 183–191. [CrossRef][PubMed]
    [Google Scholar]
  44. Yasugi M., Kubota-Koketsu R., Yamashita A., Kawashita N., Du A., Misaki R., Kuhara M., Boonsathorn N., Fujiyama K.. & other authors ( 2013;). Emerging antigenic variants at the antigenic site Sb in pandemic A(H1N1)2009 influenza virus in Japan detected by a human monoclonal antibody. . PLoS ONE 8:, e77892. [CrossRef][PubMed]
    [Google Scholar]
  45. Yiu C. P., Chen Y. W.. ( 2014;). High-quality macromolecular graphics on mobile devices: a quick starter’s guide. . Methods Mol Biol 1091:, 343–352. [CrossRef][PubMed]
    [Google Scholar]
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