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.
AuthorsSita Awasthi, John M Lubinski, Harvey M Friedman
JournalVaccine (Vaccine) Vol. 27 Issue 49 Pg. 6845-53 (Nov 16 2009) ISSN: 1873-2518 [Electronic] Netherlands
PMID19761834 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Viral
  • Herpes Simplex Virus Vaccines
  • Immunoglobulin G
  • Vaccines, Subunit
  • Viral Envelope Proteins
  • glycoprotein D, Human herpesvirus 1
  • glycoprotein gC, herpes simplex virus type 1
  • Complement C3b
  • Animals
  • Antibodies, Viral (immunology)
  • Cercopithecus aethiops
  • Complement C3b (immunology)
  • Dose-Response Relationship, Immunologic
  • Female
  • Ganglia, Spinal (immunology)
  • Herpes Simplex (immunology, prevention & control)
  • Herpes Simplex Virus Vaccines (immunology)
  • Herpesvirus 1, Human (immunology)
  • Immune Evasion
  • Immunization, Passive
  • Immunoglobulin G (immunology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutralization Tests
  • Vaccines, Subunit (immunology)
  • Vero Cells
  • Viral Envelope Proteins (immunology)

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