Methods

Vaccine Properties and Preparation—The protein kinase domain in the large subunit of viral RR1 is deleted in the recombinant HSV-2 mutant, ICP10PK, which shares homology with a highly conserved cellular protein. 18 Therefore, this mutant lacks antigens that may be tolerogenic or induce autoimmunity. This virus is growth compromised in cultured cells, mice, and guinea pigs. In cutaneous and vaginal models of HSV-2 infection, ICP10PK has prophylactic and therapeutic vaccine activity involving induction of a predominant HSV-specific TH1 response, including CD8 cytotoxic T cells. 20 A standard sterile stock containing 2105 PFU/mL, determined by plaque assay on Vero cells, was used for human vaccination as it was in earlier animal trials. Viral titers were stable for more than 2 years, as determined by plaque assay before and after completion of the vaccination program. Placebo was prepared in a similar manner, except with the omission of virus.