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Safety 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 E. K. Hildreth, Ruth A. Karron, Ann W. Funkhouser, Carl J. Friedman, Christopher S. Jones, Vasantha G. Culleton and Mary Lou Clements
The Journal of Infectious Diseases
Vol. 167, No. 3 (Mar., 1993), pp. 593-601
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30112624
Page Count: 9
You can always find the topics here!Topics: Viruses, Influenza, Vaccination, T lymphocytes, Dosage, Kinetics, Immunization, Volunteerism, Antibodies, Enzyme linked immunosorbent assay
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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 amino-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/86-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-sero-negative 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.
The Journal of Infectious Diseases © 1993 Oxford University Press