1887

Journal of General Virology header logo

Volume 98, Issue 6

and evidence of a potential A(H1N1)pdm09 antigenic drift mediated by escape mutations in the haemagglutinin Sa antigenic site Free

Abstract

Influenza A(H1N1)pdm09 virus continues to circulate worldwide without evidence of significant antigenic drift between 2009 and 2016. By using escape mutants, we previously identified six haemagglutinin (HA) changes (T80R, G143E, G158E, N159D, K166E and A198E) that were located within antigenic sites. Combinations of these mutations were introduced into the A(H1N1)pdm09 HA plasmid by mutagenesis. Reassortant 6 : 2 viruses containing both the HA and NA genes of the A(H1N1)pdm09 and the six internal gene segments of A/PR/8/34 were rescued by reverse genetics. , HA inhibition and microneutralization assays showed that the HA hexa-mutant reassortant virus (RG1) escaped A(H1N1)pdm09 hyper-immune ferret antiserum recognition. C57Black/6 mice that received the vaccine formulated with A/California/07/09 were challenged with 2×10 p.f.u. of either the 6 : 2 wild-type (WT) or RG1 viruses. Reductions in body weight loss, mortality rate and lung viral titre were observed in immunized animals challenged with the 6 : 2 WT virus compared to non-immunized mice. However, immunization did not protect mice challenged with RG1 virus. To further characterize the mutations causing this antigenic change, 11 additional RG viruses whose HA gene contained single or combinations of mutations were evaluated . Although the RG1 virus was still the least reactive against hyper-immune serum by HAI testing, mutations G158E and N159D within the Sa antigenic site appeared to play the major role in the altered antigenicity of the A(H1N1)pdm09 virus. These results show that the Sa antigenic site contains the most prominent epitopes susceptible to cause an antigenic drift, escaping actual vaccine protection.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): A(H1N1)pdm09 , drift , haemagglutinin , influenza , mutation and vaccine
© 2017 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000800
2017-06-01
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/jgv/98/6/1224.html?itemId=/content/journal/jgv/10.1099/jgv.0.000800&mimeType=html&fmt=ahah

References

  1. Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009; 360:2605–2615 [CrossRef]
     [Google Scholar]
  2. CDC Outbreak of swine-origin influenza A (H1N1) virus infection—Mexico, March—April 2009. Morb Mortal Wkly Rep 2009:467–470
     [Google Scholar]
  3. Smith GJ, Vijaykrishna D, Bahl J, Lycett SJ, Worobey M et al. Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature 2009; 459:1122–1125 [View Article][PubMed]
     [Google Scholar]
  4. Peiris JS, Poon LL, Guan Y. Emergence of a novel swine-origin influenza A virus (S-OIV) H1N1 virus in humans. J Clin Virol 2009; 45:169–173 [View Article][PubMed]
     [Google Scholar]
  5. Chambers BS, Parkhouse K, Ross TM, Alby K, Hensley SE. Identification of hemagglutinin residues responsible for H3N2 antigenic drift during the 2014–2015 Influenza season. Cell Rep 2015; 12:1–6 [View Article]
     [Google Scholar]
  6. WHO Review of the 2013–2014 winter influenza season, northern hemisphere. Wkly Epidemiol Rec 2014; 89:245–256[PubMed]
     [Google Scholar]
  7. ECDC 2016; Surveillance report—Influenza virus characterization—summary Europe—February 2016. http://ecdc.europa.eu/en/publications/Publications/influenza-virus-characterisation-september-2016.pdf
  8. Chambers C, Skowronski DM, Sabaiduc S, Winter AL, Dickinson JA et al. Interim estimates of 2015/16 vaccine effectiveness against influenza A(H1N1)pdm09, Canada, February 2016. Eurosurveillance 2016; 21:30168 [View Article]
     [Google Scholar]
  9. Koel BF, Mögling R, Chutinimitkul S, Fraaij PL, Burke DF et al. Identification of amino acid substitutions supporting antigenic change of influenza A(H1N1)pdm09 viruses. J Virol 2015; 89:3763–3775 [View Article][PubMed]
     [Google Scholar]
  10. Retamal M, Abed Y, Corbeil J, Boivin G. Epitope mapping of the 2009 pandemic and the A/Brisbane/59/2007 seasonal (H1N1) influenza virus haemagglutinins using mAbs and escape mutants. J Gen Virol 2014; 95:2377–2389 [View Article][PubMed]
     [Google Scholar]
  11. Abed Y, Goyette N, Boivin G. A reverse genetics study of resistance to neuraminidase inhibitors in an influenza A/H1N1 virus. Antivir Ther 2004; 9:577–581[PubMed]
     [Google Scholar]
  12. Robertson JS, Engelhardt OG. Developing vaccines to combat pandemic influenza. Viruses 2010; 2:532–546 [View Article][PubMed]
     [Google Scholar]
  13. Lee MS, Chen JS. Predicting antigenic variants of influenza A/H3N2 viruses. Emerg Infect Dis 2004; 10:1385–1390 [View Article][PubMed]
     [Google Scholar]
  14. Huang JW, Yang JM. Changed epitopes drive the antigenic drift for influenza A (H3N2) viruses. BMC Bioinformatics 2011; 12:S31 [View Article][PubMed]
     [Google Scholar]
  15. Igarashi M, Ito K, Yoshida R, Tomabechi D, Kida H et al. Predicting the antigenic structure of the pandemic (H1N1) 2009 influenza virus hemagglutinin. PLoS One 2010; 5:e8553 [View Article][PubMed]
     [Google Scholar]
  16. Xu H, Yang Y, Wang S, Zhu R, Qiu T et al. Predicting the mutating distribution at antigenic sites of the Influenza virus. Sci Rep 2016; 6:20239 [View Article][PubMed]
     [Google Scholar]
  17. Chen J, Yan B, Chen Q, Yao Y, Wang H et al. Evaluation of neutralizing efficacy of monoclonal antibodies specific for 2009 pandemic H1N1 influenza A virus in vitro and in vivo. Arch Virol 2014; 159:471–483 [View Article][PubMed]
     [Google Scholar]
  18. Rudneva I, Ignatieva A, Timofeeva T, Shilov A, Kushch A et al. Escape mutants of pandemic influenza A/H1N1 2009 virus: variations in antigenic specificity and receptor affinity of the hemagglutinin. Virus Res 2012; 166:61–67 [View Article][PubMed]
     [Google Scholar]
  19. Frensing T. Defective interfering viruses and their impact on vaccines and viral vectors. Biotechnol J 2015; 10:681–689 [View Article][PubMed]
     [Google Scholar]
  20. O'Donnell CD, Vogel L, Wright A, Das SR, Wrammert J et al. 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 2012; 3:e00120-12 [View Article]
     [Google Scholar]
  21. de Vries RP, de Vries E, Martínez-Romero C, Mcbride R, van Kuppeveld FJ et al. Evolution of the hemagglutinin protein of the new pandemic H1N1 influenza virus: maintaining optimal receptor binding by compensatory substitutions. J Virol 2013; 87:13868–13877 [View Article][PubMed]
     [Google Scholar]
  22. Shembekar N, Mallajosyula VV, Mishra A, Yeolekar L, Dhere R et al. Isolation of a high affinity neutralizing monoclonal antibody against 2009 pandemic H1N1 virus that binds at the 'Sa' antigenic site. PLoS One 2013; 8:e55516 [View Article][PubMed]
     [Google Scholar]
  23. Chen H, Wen X, To KK, Wang P, Tse H, Kk T et al. Quasispecies of the D225G substitution in the hemagglutinin of pandemic influenza A(H1N1) 2009 virus from patients with severe disease in Hong Kong, China. J Infect Dis 2010; 201:1517–1521 [View Article][PubMed]
     [Google Scholar]
  24. Huang KY, Rijal P, Schimanski L, Powell TJ, Lin TY et al. Focused antibody response to influenza linked to antigenic drift. J Clin Invest 2015; 125:2631–2645 [View Article][PubMed]
     [Google Scholar]
  25. Caton AJ, Brownlee GG, Yewdell JW, Gerhard W. The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell 1982; 31:417–427 [View Article][PubMed]
     [Google Scholar]
  26. Smith DJ, Lapedes AS, de Jong JC, Bestebroer TM, Rimmelzwaan GF et al. Mapping the antigenic and genetic evolution of influenza virus. Science 2004; 305:371–376 [View Article][PubMed]
     [Google Scholar]
  27. Linderman SL, Chambers BS, Zost SJ, Parkhouse K, Li Y et al. Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013-2014 influenza season. Proc Natl Acad Sci USA 2014; 111:15798–15803 [View Article][PubMed]
     [Google Scholar]
  28. Dinis JM, Florek NW, Fatola OO, Moncla LH, Mutschler JP et al. Deep sequencing reveals potential antigenic variants at low frequencies in influenza A virus-infected humans. J Virol 2016; 90:3355–3365 [View Article][PubMed]
     [Google Scholar]
  29. Nguyen HK, Nguyen PT, Nguyen TC, Hoang PV, Le TT et al. Virological characterization of influenza H1N1pdm09 in Vietnam, 2010-2013. Influenza Other Respir Viruses 2015; 9:216–224 [View Article][PubMed]
     [Google Scholar]
  30. Guarnaccia T, Carolan LA, Maurer-Stroh S, Lee RT, Job E et al. Antigenic drift of the pandemic 2009 A(H1N1) influenza virus in A ferret model. PLoS Pathog 2013; 9:e1003354 [View Article][PubMed]
     [Google Scholar]
  31. Hatakeyama S, Sakai-Tagawa Y, Kiso M, Goto H, Kawakami C et al. Enhanced expression of an α2,6-linked sialic acid on MDCK cells improves isolation of human influenza viruses and evaluation of their sensitivity to a neuraminidase inhibitor. J Clin Microbiol 2005; 43:4139–4146 [View Article][PubMed]
     [Google Scholar]
  32. WHO 2002; Manual on animal influenza diagnosis and surveillance. www.wpro.who.int/emerging_diseases/documents/docs/manualonanimalaidiagnosisandsurveillance.pdf
  33. Baz M, Paskel M, Matsuoka Y, Zengel J, Cheng X et al. Replication and immunogenicity of swine, equine, and avian H3 subtype influenza viruses in mice and ferrets. J Virol 2013; 87:6901–6910 [View Article][PubMed]
     [Google Scholar]
  34. CCAC 2014; Standards and Guidance from CCAC. www.ccac.ca/en_/
  35. Nobusawa E, Aoyama T, Kato H, Suzuki Y, Tateno Y et al. Comparison of complete amino acid sequences and receptor-binding properties among 13 serotypes of hemagglutinins of influenza A viruses. Virology 1991; 182:475–485 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000800
Loading
In vitro and in vivo evidence of a potential A(H1N1)pdm09 antigenic drift mediated by escape mutations in the haemagglutinin Sa antigenic site
J. Gen. Virol. 98, 1224 (2017); https://doi.org/10.1099/jgv.0.000800
/content/journal/jgv/10.1099/jgv.0.000800
/content/journal/jgv/10.1099/jgv.0.000800
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error