PRECLINICAL EVALUATION OF AN ALVAC (CANARYPOX)-HUMAN CYTOMEGALOVIGRUSGLYCOPROTEIN-B VACCINE CANDIDATE

Successful vaccination against the human cytomegalovirus (HCMV) requir es induction. of both neutralizing antibody and cytotoxic T lymphocyte (CTL) responses. The HCMV glycoprotein B (gB, UL55) would be one of t he most important immunogens to induce neutralizing antibodies. We tes ted the immunogenicity of art ALVAC (canarypox)-HCPAV-gB (ALVAC-gB) re combinant in mice and guinea pigs in order to provide preclinical data for a phase I clinical trial of a HCMV vaccine candidate, AL VAC is a n attenuated vaccine strain of canarypox virus which replicates produc tively in avian species but abortively in mammalian cells, The ALVAC-g B recombinant inoculated subcutaneously in mice and intramuscularly in guinea pigs induced HCMV-specific neutralizing antibodies and gB-spec ific CTL responses. Ultraviolet irradiation of the ALVAC-gB recombinan t before immunization diminished CTL responses, indicating that intrac ellular expression and processing of gB-protein were necessary for CTL induction. Prior immunity to vaccinia virus did Plot decrease immunog enicity of the ALVAC-gB recombinant in mice. Thus, despite its host ra nge restriction, ALVAC-gB is potentially capable of inducing both humo ral and cell-mediated immune responses to HCMV in both vaccinia-immune and non-immune individuals.