1887

Abstract

The zoonotic transmissions of highly pathogenic avian influenza viruses of the H5N1 subtype that have occurred since 1997 have sparked the development of novel influenza vaccines. The advent of reverse genetics technology, cell-culture production techniques and novel adjuvants has improved the vaccine strain preparation, production process and immunogenicity of the vaccines, respectively, and has accelerated the availability of pandemic influenza vaccines. However, there is still room for improvement, and alternative vaccine preparations can be explored, such as viral vectors. Modified vaccinia virus Ankara (MVA), originally developed as a safe smallpox vaccine, can be exploited as a viral vector and has many favourable properties. Recently, we have demonstrated that an MVA-based vaccine could protect mice and macaques against infection with highly pathogenic influenza viruses of the H5N1 subtype. In the present study, recombinant MVA expressing the haemagglutinin (HA) gene of pandemic influenza A/H1N1 virus was evaluated in the ferret model. A single immunization induced modest antibody responses and afforded only modest protection against the development of severe disease upon infection with a 2009(H1N1) strain. In contrast, two immunizations induced robust antibody responses and protected ferrets from developing severe disease, confirming that MVA is an attractive influenza vaccine production platform.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.024885-0
2010-11-01
2020-01-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/11/2745.html?itemId=/content/journal/jgv/10.1099/vir.0.024885-0&mimeType=html&fmt=ahah

References

  1. Bodewes, R., Rimmelzwaan, G. F. & Osterhaus, A. D. ( 2010; ). Animal models for the preclinical evaluation of candidate influenza vaccines. Expert Rev Vaccines 9, 59–72.[CrossRef]
    [Google Scholar]
  2. Collin, N. & de Radiguès, X., World Health Organization H1N1 Vaccine Task Force ( 2009; ). Vaccine production capacity for seasonal and pandemic (H1N1) 2009 influenza. Vaccine 27, 5184–5186.[CrossRef]
    [Google Scholar]
  3. Czub, M., Weingartl, H., Czub, S., He, R. & Cao, J. ( 2005; ). Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets. Vaccine 23, 2273–2279.[CrossRef]
    [Google Scholar]
  4. de Wit, E., Kawaoka, Y., de Jong, M. D. & Fouchier, R. A. ( 2008; ). Pathogenicity of highly pathogenic avian influenza virus in mammals. Vaccine 26, D54–D58.[CrossRef]
    [Google Scholar]
  5. Drexler, I., Staib, C. & Sutter, G. ( 2004; ). Modified vaccinia virus Ankara as antigen delivery system: how can we best use its potential? Curr Opin Biotechnol 15, 506–512.[CrossRef]
    [Google Scholar]
  6. Falkner, F. G. & Moss, B. ( 1990; ). Transient dominant selection of recombinant vaccinia viruses. J Virol 64, 3108–3111.
    [Google Scholar]
  7. Fouchier, R. A., Schneeberger, P. M., Rozendaal, F. W., Broekman, J. M., Kemink, S. A., Munster, V., Kuiken, T., Rimmelzwaan, G. F., Schutten, M. & other authors ( 2004; ). Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci U S A 101, 1356–1361.[CrossRef]
    [Google Scholar]
  8. IFPMA ( 2009; ). Authoritative new study reveals global pandemic influenza vaccine capacity. http://www.ifpma.org/pdf/2009_04_21_Release_IVS_Wyman_Capacity_24Feb09.pdf. Accessed 20 May 2010. Geneva: International Federation of Pharmaceutical Manufacturers & Associations.
  9. Jakeman, K. J., Smith, H. & Sweet, C. ( 1989; ). Mechanism of immunity to influenza: maternal and passive neonatal protection following immunization of adult ferrets with a live vaccinia-influenza virus haemagglutinin recombinant but not with recombinants containing other influenza virus proteins. J Gen Virol 70, 1523–1531.[CrossRef]
    [Google Scholar]
  10. Kobinger, G. P., Meunier, I., Patel, A., Pillet, S., Gren, J., Stebner, S., Leung, A., Neufeld, J. L., Kobasa, D. & other authors ( 2010; ). Assessment of the efficacy of commercially available and candidate vaccines against a pandemic H1N1 2009 virus. J Infect Dis 201, 1000–1006.[CrossRef]
    [Google Scholar]
  11. Koopmans, M., Wilbrink, B., Conyn, M., Natrop, G., van der Nat, H., Vennema, H., Meijer, A., van Steenbergen, J., Fouchier, R. & other authors ( 2004; ). Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Lancet 363, 587–593.[CrossRef]
    [Google Scholar]
  12. Kreijtz, J. H., Suezer, Y., van Amerongen, G., de Mutsert, G., Schnierle, B. S., Wood, J. M., Kuiken, T., Fouchier, R. A., Lower, J. & other authors ( 2007; ). Recombinant modified vaccinia virus Ankara-based vaccine induces protective immunity in mice against infection with influenza virus H5N1. J Infect Dis 195, 1598–1606.[CrossRef]
    [Google Scholar]
  13. Kreijtz, J. H., Suezer, Y., de Mutsert, G., van Amerongen, G., Schwantes, A., van den Brand, J. M., Fouchier, R. A., Lower, J., Osterhaus, A. D. & other authors ( 2009a; ). MVA-based H5N1 vaccine affords cross-clade protection in mice against influenza A/H5N1 viruses at low doses and after single immunization. PLoS One 4, e7790.[CrossRef]
    [Google Scholar]
  14. Kreijtz, J. H., Suezer, Y., de Mutsert, G., van den Brand, J. M., van Amerongen, G., Schnierle, B. S., Kuiken, T., Fouchier, R. A., Lower, J. & other authors ( 2009b; ). Recombinant modified vaccinia virus Ankara expressing the hemagglutinin gene confers protection against homologous and heterologous H5N1 influenza virus infections in macaques. J Infect Dis 199, 405–413.[CrossRef]
    [Google Scholar]
  15. Kreijtz, J. H. C. M., Osterhaus, A. D. M. E. & Rimmelzwaan, G. F. ( 2009c; ). Vaccination strategies and vaccine formulations for epidemic and pandemic influenza control. Hum Vaccin 5, 126–135.[CrossRef]
    [Google Scholar]
  16. Lehmann, M. H., Kastenmuller, W., Kandemir, J. D., Brandt, F., Suezer, Y. & Sutter, G. ( 2009; ). Modified vaccinia virus ankara triggers chemotaxis of monocytes and early respiratory immigration of leukocytes by induction of CCL2 expression. J Virol 83, 2540–2552.[CrossRef]
    [Google Scholar]
  17. Maher, J. A. & DeStefano, J. ( 2004; ). The ferret: an animal model to study influenza virus. Lab Anim (NY) 33, 50–53.[CrossRef]
    [Google Scholar]
  18. Mayr, A. & Danner, K. ( 1978; ). Vaccination against pox diseases under immunosuppressive conditions. Dev Biol Stand 41, 225–234.
    [Google Scholar]
  19. Munster, V. J., de Wit, E., van den Brand, J. M., Herfst, S., Schrauwen, E. J., Bestebroer, T. M., van de Vijver, D., Boucher, C. A., Koopmans, M. & other authors ( 2009; ). Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets. Science 325, 481–483.
    [Google Scholar]
  20. Palmer, D. F., Dowle, W., Coleman, M. & Schild, G. ( 1975; ). Haemagglutination inhibition test. In Advanced Laboratory Techniques for Influenza Diagnosis (Procedural Guide, Immunology Series, no. 6), pp. 25–62. Atlanta, GA. : US Department of Health, Education and Welfare, Public Heath Service and Center for Disease Control.
    [Google Scholar]
  21. Rimmelzwaan, G. F. & Sutter, G. ( 2009; ). Candidate influenza vaccines based on recombinant modified vaccinia virus Ankara. Expert Rev Vaccines 8, 447–454.[CrossRef]
    [Google Scholar]
  22. Rimmelzwaan, G. F., Baars, M., Claas, E. C. & Osterhaus, A. D. ( 1998; ). Comparison of RNA hybridization, hemagglutination assay, titration of infectious virus and immunofluorescence as methods for monitoring influenza virus replication in vitro. J Virol Methods 74, 57–66.[CrossRef]
    [Google Scholar]
  23. Rimmelzwaan, G. F., Baars, M., van Beek, R., de Lijster, P., de Jong, J. C., Claas, E. C. & Osterhaus, A. D. ( 1999; ). Influenza virus subtype cross-reactivities of haemagglutination inhibiting and virus neutralising serum antibodies induced by infection or vaccination with an ISCOM-based vaccine. Vaccine 17, 2512–2516.[CrossRef]
    [Google Scholar]
  24. Schmeisser, F., Vodeiko, G. M., Lugovtsev, V. Y., Stout, R. R. & Weir, J. P. ( 2010; ). An alternative method for preparation of pandemic influenza strain-specific antibody for vaccine potency determination. Vaccine 28, 2442–2449.[CrossRef]
    [Google Scholar]
  25. Staib, C., Lowel, M., Erfle, V. & Sutter, G. ( 2003; ). Improved host range selection for recombinant modified vaccinia virus Ankara. Biotechniques 34, 694–696, 698, 700.
    [Google Scholar]
  26. Stephenson, I., Hayden, F., Osterhaus, A., Howard, W., Pervikov, Y., Palkonyay, L. & Kieny, M. P. ( 2010; ). Report of the fourth meeting on ‘Influenza vaccines that induce broad spectrum and long-lasting immune responses', World Health Organization and Wellcome Trust, London, United Kingdom, 9–10 November 2009. Vaccine 28, 3875–3882.[CrossRef]
    [Google Scholar]
  27. Stittelaar, K. J., Kuiken, T., de Swart, R. L., van Amerongen, G., Vos, H. W., Niesters, H. G., van Schalkwijk, P., van der Kwast, T., Wyatt, L. S. & other authors ( 2001; ). Safety of modified vaccinia virus Ankara (MVA) in immune-suppressed macaques. Vaccine 19, 3700–3709.[CrossRef]
    [Google Scholar]
  28. Sutter, G., Wyatt, L. S., Foley, P. L., Bennink, J. R. & Moss, B. ( 1994; ). A recombinant vector derived from the host range-restricted and highly attenuated MVA strain of vaccinia virus stimulates protective immunity in mice to influenza virus. Vaccine 12, 1032–1040.[CrossRef]
    [Google Scholar]
  29. van den Brand, J. M., Stittelaar, K. J., van Amerongen, G., Rimmelzwaan, G. F., Simon, J., de Wit, E., Munster, V., Bestebroer, T., Fouchier, R. A. & other authors ( 2010; ). Severity of pneumonia due to new H1N1 influenza virus in ferrets is intermediate between that due to seasonal H1N1 virus and highly pathogenic avian influenza H5N1 virus. J Infect Dis 201, 993–999.[CrossRef]
    [Google Scholar]
  30. van Riel, D., Munster, V. J., de Wit, E., Rimmelzwaan, G. F., Fouchier, R. A., Osterhaus, A. D. & Kuiken, T. ( 2006; ). H5N1 virus attachment to lower respiratory tract. Science 312, 399.[CrossRef]
    [Google Scholar]
  31. Waibler, Z., Anzaghe, M., Ludwig, H., Akira, S., Weiss, S., Sutter, G. & Kalinke, U. ( 2007; ). Modified vaccinia virus Ankara induces Toll-like receptor-independent type I interferon responses. J Virol 81, 12102–12110.[CrossRef]
    [Google Scholar]
  32. Weingartl, H., Czub, M., Czub, S., Neufeld, J., Marszal, P., Gren, J., Smith, G., Jones, S., Proulx, R. & other authors ( 2004; ). Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J Virol 78, 12672–12676.[CrossRef]
    [Google Scholar]
  33. Whitley, R. J. ( 2010; ). Of ferrets and humans: influenza pathogenesis. J Infect Dis 201, 976–977.[CrossRef]
    [Google Scholar]
  34. WHO ( 2009; ). World now at the start of 2009 influenza pandemic. http://www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/index.html. Accessed 11 June 2009. Geneva: World Health Organization.
  35. WHO ( 2010a; ). Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. http://www.who.int/csr/disease/avian_influenza/country/cases_table_2010_05_06/en/index.html. Accessed 6 May 2010. Geneva: World Health Organization.
  36. WHO ( 2010b; ). Antigenic and genetic characteristics of influenza A(H5N1) and influenza A(H9N2) viruses and candidate vaccine viruses developed for potential use in human vaccines. http://www.who.int/csr/disease/avian_influenza/guidelines/201002_H5_H9_VaccineVirusUpdate.pdf. Geneva: World Health Organization.
  37. Wyatt, L. S., Shors, S. T., Murphy, B. R. & Moss, B. ( 1996; ). Development of a replication-deficient recombinant vaccinia virus vaccine effective against parainfluenza virus 3 infection in an animal model. Vaccine 14, 1451–1458.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.024885-0
Loading
/content/journal/jgv/10.1099/vir.0.024885-0
Loading

Data & Media loading...

Most cited articles

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