1887

Abstract

The emergence of influenza A H7N9 in infection has posed a great threat to public health globally. Poor immunogenicity of H7N9 haemagglutinin (HA) is a major obstacle to the development of an effective H7N9 vaccine. Here, we found that the vaccine containing the H7HA head conjugated with IgG Fc (Hd-Fc) induced strong neutralizing antibody responses and protection against H7N9 infection, whilst the Fc-conjugated H7HA stalk (St-Fc)-based vaccine could not induce neutralizing antibodies, although the St-Fc-immunized mice were partially protected. The vaccines containing the full-length extracellular domain of HA conjugated with Fc and the mixture of Hd-Fc plus St-Fc induced significantly lower neutralizing antibody and haemagglutination inhibition titres than the Hd-Fc-based vaccine. These results suggest that the St-Fc may have inhibitory effects on the neutralizing immunogenicity of Hd-Fc. Therefore, the neutralizing domain(s), such as the receptor-binding domain, in the HA head should be kept and the non-neutralizing domain(s) in the HA stalk with the ability to potentially suppress the neutralizing immunogenicity of HA head should be removed from Fc-conjugated HA-based influenza vaccines to increase the neutralizing antibody response.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000365
2016-02-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/97/2/327.html?itemId=/content/journal/jgv/10.1099/jgv.0.000365&mimeType=html&fmt=ahah

References

  1. Bart S. A., Hohenboken M., la Cioppa G., Narasimhan V., Dormitzer P. R., Kanesa-thasan N. 2014; A cell culture-derived MF59-adjuvanted pandemic A/H7N9 vaccine is immunogenic in adults. Sci Transl Med 6:234ra55 [CrossRef]
    [Google Scholar]
  2. Bommakanti G., Citron M. P., Hepler R. W., Callahan C., Heidecker G. J., Najar T. A., Lu X., Joyce J. G., Shiver J. W., other authors. 2010; Design of an HA2-based Escherichia coli expressed influenza immunogen that protects mice from pathogenic challenge. Proc Natl Acad Sci U S A 107:13701–13706 [View Article][PubMed]
    [Google Scholar]
  3. Colman P. M., Lawrence M. C. 2003; The structural biology of type I viral membrane fusion. Nat Rev Mol Cell Biol 4:309–319 [View Article][PubMed]
    [Google Scholar]
  4. Du L., Zhao G., He Y., Guo Y., Zheng B. J., Jiang S., Zhou Y. 2007; Receptor-binding domain of SARS-CoV spike protein induces long-term protective immunity in an animal model. Vaccine 25:2832–2838 [View Article][PubMed]
    [Google Scholar]
  5. Du L., Zhao G., Lin Y., Sui H., Chan C., Ma S., He Y., Jiang S., Wu C., other authors. 2008; Intranasal vaccination of recombinant adeno-associated virus encoding receptor-binding domain of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein induces strong mucosal immune responses and provides long-term protection against SARS-CoV infection. J Immunol 180:948–956 [View Article][PubMed]
    [Google Scholar]
  6. Du L., He Y., Zhou Y., Liu S., Zheng B. J., Jiang S. 2009; The spike protein of SARS-CoV – a target for vaccine and therapeutic development. Nat Rev Microbiol 7:226–236 [View Article][PubMed]
    [Google Scholar]
  7. Du L., Zhao G., Zhang X., Liu Z., Yu H., Zheng B. J., Zhou Y., Jiang S. 2010; Development of a safe and convenient neutralization assay for rapid screening of influenza HA-specific neutralizing monoclonal antibodies. Biochem Biophys Res Commun 397:580–585 [View Article][PubMed]
    [Google Scholar]
  8. Du L., Kou Z., Ma C., Tao X., Wang L., Zhao G., Chen Y., Yu F., Tseng C. T., other authors. 2013a; A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines. PLoS One 8:e81587 [View Article][PubMed]
    [Google Scholar]
  9. Du L. Y., Zhao G. Y., Kou Z. H., Ma C. Q., Sun S. H., Poon V. K. M., Lu L., Wang L. L., Debnath A. K., other authors. 2013b; Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development. J Virol 87:9939–9942 [CrossRef]
    [Google Scholar]
  10. Du L., Zhao G., Sun S., Zhang X., Zhou X., Guo Y., Li Y., Zhou Y., Jiang S. 2013c; A critical HA1 neutralizing domain of H5N1 influenza in an optimal conformation induces strong cross-protection. PLoS One 8:e53568 [View Article][PubMed]
    [Google Scholar]
  11. Fries L. F., Smith G. E., Glenn G. M. 2013; A recombinant virus like particle influenza A (H7N9) vaccine. N Engl J Med 369:2564–2566 [View Article][PubMed]
    [Google Scholar]
  12. He Y., Zhou Y., Liu S., Kou Z., Li W., Farzan M., Jiang S. 2004; Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine. Biochem Biophys Res Commun 324:773–781 [View Article][PubMed]
    [Google Scholar]
  13. Khurana S., Loving C. L., Manischewitz J., King L. R., Gauger P. C., Henningson J., Vincent A. L., Golding H. 2013; Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease. Sci Transl Med 5:200ra114
    [Google Scholar]
  14. Li Q., Zhou L., Zhou M., Chen Z., Li F., Wu H., Xiang N., Chen E., Tang F., other authors. 2014; Epidemiology of human infections with avian influenza A(H7N9) virus in China. N Engl J Med 370:520–532 [View Article][PubMed]
    [Google Scholar]
  15. Liang X. F., Wang H. Q., Wang J. Z., Fang H. H., Wu J., Zhu F. C., Li R. C., Xia S. L., Zhao Y. L., other authors. 2010; Safety and immunogenicity of 2009 pandemic influenza A H1N1 vaccines in China: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 375:56–66 [View Article][PubMed]
    [Google Scholar]
  16. Ma C., Li Y., Wang L., Zhao G., Tao X., Tseng C. T. K., Zhou Y., Du L., Jiang S. 2014; Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: implication for designing novel mucosal MERS vaccines. Vaccine 32:2100–2108 [View Article][PubMed]
    [Google Scholar]
  17. Mastelic Gavillet B., Eberhardt C. S., Auderset F., Castellino F., Seubert A., Tregoning J. S., Lambert P. H., de Gregorio E., Del Giudice G., Siegrist C. A. 2015; MF59 mediates its B cell adjuvanticity by promoting T follicular helper cells and thus germinal center responses in adult and early life. J Immunol 194:4836–4845 [View Article][PubMed]
    [Google Scholar]
  18. Mulligan M. J., Bernstein D. I., Winokur P., Rupp R., Anderson E., Rouphael N., Dickey M., Stapleton J. T., Edupuganti S., other authors. 2014; Serological responses to an avian influenza A/H7N9 vaccine mixed at the point-of-use with MF59 adjuvant: a randomized clinical trial. JAMA 312:1409–1419 [View Article][PubMed]
    [Google Scholar]
  19. Patel A., Gray M., Li Y., Kobasa D., Yao X., Kobinger G. P. 2012; Co-administration of certain DNA vaccine combinations expressing different H5N1 influenza virus antigens can be beneficial or detrimental to immune protection. Vaccine 30:626–636 [View Article][PubMed]
    [Google Scholar]
  20. Qi Z., Pan C., Lu H., Shui Y., Li L., Li X., Xu X., Liu S., Jiang S. 2010; A recombinant mimetics of the HIV-1 gp41 prehairpin fusion intermediate fused with human IgG Fc fragment elicits neutralizing antibody response in the vaccinated mice. Biochem Biophys Res Commun 398:506–512 [View Article][PubMed]
    [Google Scholar]
  21. Qiu C., Huang Y., Zhang A., Tian D., Wan Y., Zhang X., Zhang W., Zhang Z., Yuan Z., other authors. 2013; Safe pseudovirus-based assay for neutralization antibodies against influenza A(H7N9) virus. Emerg Infect Dis 19:1685–1687 [View Article][PubMed]
    [Google Scholar]
  22. Rao S. S., Kong W. P., Wei C. J., Van Hoeven N., Gorres J. P., Nason M., Andersen H., Tumpey T. M., Nabel G. J. 2010; Comparative efficacy of hemagglutinin, nucleoprotein, and matrix 2 protein gene-based vaccination against H5N1 influenza in mouse and ferret. PLoS One 5:e9812 [View Article][PubMed]
    [Google Scholar]
  23. Steel J., Lowen A. C., Wang T. T., Yondola M., Gao Q., Haye K., García-Sastre A., Palese P. 2010; Influenza virus vaccine based on the conserved hemagglutinin stalk domain. MBio 1:e00018-10 [View Article][PubMed]
    [Google Scholar]
  24. WHO 2011 Manual for the Laboratory Diagnosis and Virological Surveillance of Influenza Geneva: WHO; http://www.who.int/influenza/gisrs_laboratory/manual_diagnosis_surveillance_influenza/en/
    [Google Scholar]
  25. [Google Scholar]
  26. Yu F., Li Y., Guo Y., Wang L., Yang J., Zhao G., Zhou Y., Du L., Jiang S. 2015; Intranasal vaccination of recombinant H5N1 HA1 protein fused with foldon and Fc induces strong mucosal immune responses with neutralizing activity: implications for developing novel mucosal influenza vaccines. Hum Vaccin Immunother. [View Article]
    [Google Scholar]
  27. Zhang M. Y., Wang Y., Mankowski M. K., Ptak R. G., Dimitrov D. S. 2009; Cross-reactive HIV-1-neutralizing activity of serum IgG from a rabbit immunized with gp41 fused to IgG1 Fc: possible role of the prolonged half-life of the immunogen. Vaccine 27:857–863 [View Article][PubMed]
    [Google Scholar]
  28. Zhang Q., Shi J., Deng G., Guo J., Zeng X., He X., Kong H., Gu C., Li X., other authors. 2013; H7N9 influenza viruses are transmissible in ferrets by respiratory droplet. Science 341:410–414 [View Article][PubMed]
    [Google Scholar]
  29. Zhang N., Channappanavar R., Ma C., Wang L., Tang J., Garron T., Tao X., Tasneem S., Lu L., other authors. 2015; Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus. Cell Mol Immunol. [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000365
Loading
/content/journal/jgv/10.1099/jgv.0.000365
Loading

Data & Media loading...

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