Immunization with a Dominant-Negative Recombinant HSV Type 1 Protects against HSV-1 Skin Disease in Guinea Pigs

CJ9-gD belongs to a new class of replication-defective recombinant herpes simplex viruses (HSVs) type 1 that can function in trans to prevent the replication of wild-type HSV in co-infected cells. Furthermore, CJ9-gD cannot establish latent infection in vivo and it expresses high levels of the major HSV-1 antigen glycoprotein D immediately following infection. In this study we show that guinea pigs immunized with CJ9-gD developed at least 9,600-fold higher titers of HSV-1-specific neutralization antibodies than mock-immunized controls. After challenge with wild-type HSV-1, all 10 mock-immunized guinea pigs developed multiple skin lesions with an average of 53.3 lesions per animal, whereas only 2 minor lesions were found in 1 of 10 CJ9-gD-immunized animals, representing a 267-fold reduction on the incidence of primary herpetic skin lesions in immunized animals. Quantitative PCR analysis revealed that the amount and frequency of wild-type HSV-1 viral DNA present in dorsal root ganglia of immunized animals was significantly lower than that in mock-immunized controls. Collectively, we demonstrate that vaccination with CJ9-gD elicits strong and protective immune responses against primary HSV-1 skin disease and reduces the extent of latent infection by challenge virus.