Implications for herpes simplex virus vaccine strategies based on antibodies produced to herpes simplex virus type 1 glycoprotein gC immune evasion domains

Herpes simplex virus type I (HSV-1) glycoprotein gC (gC-1) is an immune evasion molecule that inhibits complement activation by binding C3b. Three assays were used to assess whether IgG antibodies produced by HSV-1 infection in humans block the interaction between C3b and gC-1. In two assays human IgG had no effect, while in one assay IgG partially inhibited C3b binding, which occurred at IgG concentrations approaching the upper limits of those found in human serum. Mice infected with HSV-1 produced antibodies that partially blocked C3b binding at lower IgG concentrations than human IgG. Importantly, gC-1 immunization in mice produced higher titers of gC-1 antibodies than infection. We previously reported that gC-1 immunization in mice totally blocks C3b binding and reduces disease severity. Therefore, gC-1 immunization in humans may also induce blocking antibodies that modify disease, despite the rather limited ability of infection to produce these antibodies.