Preclinical evaluation of an ALVAC (canarypox)--human cytomegalovirus glycoprotein B vaccine candidate.
Successful vaccination against the human cytomegalovirus (HCMV) requires induction of both neutralizing antibody and cytotoxic T lymphocyte (CTL) responses. The HCMV glycoprotein B (gB, UL55) would be one of the most important immunogens to induce neutralizing antibodies. We tested the immunogenicity of an ALVAC (canarypox)-HCMV-gB (ALVAC-gB) recombinant in mice and guinea pigs in order to provide preclinical data for a phase I clinical trial of a HCMV vaccine candidate. ALVAC is an attenuated vaccine strain of canarypox virus which replicates productively in avian species but abortively in mammalian cells. The ALVAC-gB recombinant inoculated subcutaneously in mice and intramuscularly in guinea pigs induced HCMV-specific neutralizing antibodies and gB-specific CTL responses. Ultraviolet irradiation of the ALVAC-gB recombinant before immunization diminished CTL responses, indicating that intracellular expression and processing of gB-protein were necessary for CTL induction. Prior immunity to vaccinia virus did not decrease immunogenicity of the ALVAC-gB recombinant in mice. Thus, despite its host range restriction, ALVAC-gB is potentially capable of inducing both humoral and cell-mediated immune responses to HCMV in both vaccinia-immune and non-immune individuals.
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003587:Cytomegalovirus / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D008808:Mice, Inbred CBA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C040495:glycoprotein B, Simplexvirus