Fety and immunogenicity of a recombinant protein influenza A vaccine in adult human volunteers and protective efficacy against wild-type H1N1 virus challenge

Louis F. Fries, Susan B. Dillon, James Hildreth, Ruth A. Karron, Ann W. Funkhouser, Carl J. Friedman, Christopher S. Jones, Vasantha G. Culleton, Mary Lou Clements

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

A recombinant influenza A vaccine (D protein), comprising a carboxy-terminal sequence from the hemagglutinin HA2 subunit of A/Puerto Rico/8/34 virus (H1N1, A/PR/34) fused to 81 ammo-terminal residues of the NS1 nonstructural protein, has previously protected mice against influenza A challenge by inducing H1N1/H2N2 cross-reactive cytotoxic T cells (CTL) without hemagglutination-inhibiting (HI) or neutralizing antibody. In our dose-escalating study, the vaccine was safe in humans and induced both IgG and T cell proliferative responses to D protein but little antibody to A/PR/34 or A/Kawasaki/8/86 (H1N1, A/KW/86) viruses. Among an additional group of A/KW/So-Seronegative volunteers immunized with 500 μg of D protein, none had a rise in serum HI or neutralizing antibody to A/KW/86, 20% had minimal IgG responses to A/KW/86 by EIA, and a minority had any increase in A/KW/86-specific CTL activity. However, viral shedding and clinical illness score were reduced in vaccinees relative to A/KW/86-seronegative unimmunized controls after intranasal challenge with wild-type A/KW/86. D protein immunization conferred significant protective immunity not currently explained by any of the immune parameters measured.

Original languageEnglish (US)
Pages (from-to)593-601
Number of pages9
JournalJournal of Infectious Diseases
Volume167
Issue number3
StatePublished - Mar 1993
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Public Health, Environmental and Occupational Health

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    Fries, L. F., Dillon, S. B., Hildreth, J., Karron, R. A., Funkhouser, A. W., Friedman, C. J., Jones, C. S., Culleton, V. G., & Clements, M. L. (1993). Fety and immunogenicity of a recombinant protein influenza A vaccine in adult human volunteers and protective efficacy against wild-type H1N1 virus challenge. Journal of Infectious Diseases, 167(3), 593-601.