Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin

Langzhou Song, Yi Zhang, Nadezhda E. Yun, Allison L. Poussard, Jeanon N. Smith, Jennifer K. Smith, Viktoriya Borisevich, Jenna J. Linde, Michele A. Zacks, Hong Li, Uma Kavita, Lucia Reiserova, Xiangyu Liu, Kunmi Dumuren, Bhuvaneswari Balasubramanian, Bruce Weaver, Jason Parent, Scott Umlauf, Ge Liu, Jim HuleattLynda Tussey, Slobodan Paessler

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Transmission of highly pathogenic avian influenza (HPAI) between birds and humans is an ongoing threat that holds potential for the emergence of a pandemic influenza strain. A major barrier to an effective vaccine against avian influenza has been the generally poor immunopotency of many of the HPAI strains coupled with the manufacturing constraints employing conventional methodologies. Fusion of flagellin, a toll-like receptor-5 ligand, to vaccine antigens has been shown to enhance the immune response to the fused antigen in preclinical studies. Here, we have evaluated the immunogenicity and efficacy of a panel of flagellin-based hemagglutinin (HA) globular head fusion vaccines in inbred mice. The HA globular head of these vaccines is derived from the A/Vietnam/1203/04 (VN04; H5N1) HA molecule. We find that replacement of domain D3 of flagellin with the VN04 HA globular head creates a highly effective vaccine that elicits protective HAI titers which protect mice against disease and death in a lethal challenge model.

Original languageEnglish (US)
Pages (from-to)5875-5884
Number of pages10
JournalVaccine
Volume27
Issue number42
DOIs
StatePublished - Sep 25 2009

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Keywords

  • Avian flu vaccine
  • HA globular head
  • Prokaryotic production

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Song, L., Zhang, Y., Yun, N. E., Poussard, A. L., Smith, J. N., Smith, J. K., Borisevich, V., Linde, J. J., Zacks, M. A., Li, H., Kavita, U., Reiserova, L., Liu, X., Dumuren, K., Balasubramanian, B., Weaver, B., Parent, J., Umlauf, S., Liu, G., ... Paessler, S. (2009). Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin. Vaccine, 27(42), 5875-5884. https://doi.org/10.1016/j.vaccine.2009.07.060