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

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.