Immunization with HSV-1 glycoprotein C prevents immune evasion from complement and enhances the efficacy of an HSV-1 glycoprotein D subunit vaccine

Herpes simplex virus type 1 (HSV-1) glycoprotein C (gC-1) binds complement component C3b and inhibits complement-mediated immunity. HSV-1 glycoprotein D (gD-1) is a potent immunogen and a candidate antigen for a subunit vaccine. We evaluated whether combined immunization with gD-1 and gC-1 provides better protection against challenge than gD-1 alone based on antibodies to gC-1 preventing HSV-1-mediated immune evasion. IgG purified from mice immunized with gC-1 blocked C3b binding to gC-1 and greatly increased neutralization by gD-1 IgG in the presence of complement. Passive transfer of gC-1 IgG protected complement intact mice against HSV-1 challenge but not C3 knockout mice, indicating that gC-1 antibody activity in vivo is complement-dependent. Immunizing mice with gD-1 and gC-1 provided better protection than gD-1 alone in preventing zosteriform disease and infection of dorsal root ganglia. Therefore, gC-1 immunization prevents HSV-1 evasion from complement and enhances the protection provided by gD-1 immunization.