Safety and Immunogenicity of a Recombinant Protein Influenza A Vaccine in Adult Human Volunteers and Protective Efficacy against Wild-Type H1N1 Virus Challenge

• Published in: The Journal of infectious diseases 1993-03, Vol.167 (3), p.593-601
• Main Authors: Fries, Louis F., Dillon, Susan B., Hildreth, James E. K., Karron, Ruth A., Funkhouser, Ann W., Friedman, Carl J., Jones, Christopher S., Culleton, Vasantha G., Clements, Mary Lou
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Analysis of Variance; Antibodies; Antibodies, Viral - biosynthesis; Biological and medical sciences; Cohort Studies; Dosage; Dose-Response Relationship, Immunologic; Enzyme linked immunosorbent assay; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins, Viral - adverse effects; Hemagglutinins, Viral - immunology; Human viral diseases; Humans; Immunity, Cellular; Immunization; Immunoglobulin G - biosynthesis; Infectious diseases; Influenza A virus; Influenza A virus - immunology; Influenza A Virus, H1N1 Subtype; Influenza Vaccines - adverse effects; Influenza Vaccines - immunology; Influenza, Human - prevention & control; Kinetics; Lymphocyte Activation; Major Articles; Medical sciences; Middle Aged; Recombinant Proteins; T lymphocytes; T-Lymphocytes, Cytotoxic; Time Factors; Vaccination; Vaccines, Synthetic - adverse effects; Vaccines, Synthetic - immunology; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Viral Envelope Proteins - immunology; Viral Proteins - adverse effects; Viral Proteins - immunology; Virus Shedding; Viruses; Volunteerism
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/167.3.593

A recombinant influenza A vaccine (D protein), comprising a carboxy-terminal sequence from the hemagglutinin HA2 subunit of A/Puerto Rico/8/34 virus (HINl, A/PR/34) fused to 81 amino-terminal residues of the NSI nonstructural protein, has previously protected mice against influenza A challenge by inducing HINl/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/Kawasakij8/86 (HINl, 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-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.