title: Safety and immunogenicity of a recombinant protein influenza A vaccine in adult human volunteers and protective efficacy against wild-type H1N1 virus challenge.
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 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 micrograms 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 vaccines 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.
authors.affiliation: Department of International Health, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205.
authors.forename: L F
authors.initials: LF
authors.lastname: Fries
authors.forename: S B
authors.initials: SB
authors.lastname: Dillon
authors.forename: J E
authors.initials: JE
authors.lastname: Hildreth
authors.forename: R A
authors.initials: RA
authors.lastname: Karron
authors.forename: A W
authors.initials: AW
authors.lastname: Funkhouser
authors.forename: C J
authors.initials: CJ
authors.lastname: Friedman
authors.forename: C S
authors.initials: CS
authors.lastname: Jones
authors.forename: V G
authors.initials: VG
authors.lastname: Culleton
authors.forename: M L
authors.initials: ML
authors.lastname: Clements
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000914:Antibodies, Viral / Q000096:biosynthesis*; D015331:Cohort Studies; D004306:Dose-Response Relationship, Immunologic; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis; D053118:Influenza A Virus, H1N1 Subtype; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008213:Lymphocyte Activation; D008875:Middle Aged; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology; D014764:Viral Proteins / Q000009:adverse effects / Q000276:immunology*; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; C079937:D protein, influenza A (A-PR-8-34-derived recombinant protein); D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014764:Viral Proteins