Immunization with a dominant-negative recombinant Herpes Simplex Virus (HSV) type 1 protects against HSV-2 genital disease in guinea pigs

Animals immunized with CJ9-gD developed at least 700-fold higher titers of HSV-2-specific neutralization antibodies than mock-immunized controls. After challenge with wild-type HSV-2, all 10 control guinea pigs developed multiple genital lesions with an average of 21 lesions per animal. In contrast, only 2 minor lesions were found in 2 of 8 CJ9-gD-immunized animals, representing a 40-fold reduction on the incidence of primary genital lesions in immunized animals (p < 0.0001). Immunization significantly reduced the amount and duration of viral shedding and provided complete protection against neurological symptoms, while 90% of mock-immunized animals succumbed due to the severity of disease. Importantly, immunized animals showed no signs of recurrent disease or viral shedding during a 60-days observation period after recovery from primary infection, and carried 50-fold less latent viral DNA load in their dorsal root ganglia than the surviving mock-vaccinated controls (p < 0.0001).Collectively, we demonstrate that vaccination with the HSV-1 recombinant CJ9-gD elicits strong and protective immune responses against primary and recurrent HSV-2 genital disease and significantly reduces the extent of latent infection.Genital herpes is the main cause of genital ulcer disease worldwide and is due to infections with herpes simplex virus (HSV) [1,2]. HSV-2 accounts for most cases of genital herpes [3]. Recent studies indicate that in developed countries HSV-1 has become the main causative agent for primary genital herpes, especially among adolescents, women, and homosexual men [4-7]. The prevalence of HSV-2 in the general population ranges from 10%-60%, indicating that genital herpes is one of the most common sexually transmitted diseases [2,8].After primary genital infection, HSV establishes latent infection in dorsal root ganglia with lifelong persistence, subsequently giving rise to intermittent reactivation and recurrent disease [9]. As the clinical appearance of genital H