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.
Awasthi
Sita
S
Infectious Disease Division, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6073, United States. sawasthi@mail.med.upenn.edu
Lubinski
John M
JM
Friedman
Harvey M
HM
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002522:Chlorocebus aethiops; D003179:Complement C3b / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005727:Ganglia, Spinal / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology; D057131:Immune Evasion; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009500:Neutralization Tests; D022223:Vaccines, Subunit / Q000276:immunology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D022301:Herpes Simplex Virus Vaccines; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; C038535:glycoprotein gC, herpes simplex virus type 1; D003179:Complement C3b