Abstract
BackgroundCJ9-gD is a novel dominant-negative recombinant herpes simplex virus type 1 (HSV-1) that is completely replication-defective, cannot establish detectable latent infection in vivo, and expresses high levels of the major HSV-1 antigen glycoprotein D immediately following infection. In the present study, CJ9-gD was evaluated as a vaccine against HSV-2 genital infection in guinea pigs.ResultsAnimals 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).ConclusionsCollectively, 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.
Highlights
CJ9-gD is a novel dominant-negative recombinant herpes simplex virus type 1 (HSV-1) that is completely replication-defective, cannot establish detectable latent infection in vivo, and expresses high levels of the major HSV-1 antigen glycoprotein D immediately following infection
We investigate whether CJ9-gD can serve as an effective vaccine in protection against both primary and recurrent HSV-2 genital infection and disease in guinea pigs following intravaginal challenge with wild-type HSV-2
Induction of HSV-2-specific neutralization antibodies The ability of CJ9-gD to elicit HSV-2-specific neutralizing antibodies was determined (Fig. 1)
Summary
CJ9-gD is a novel dominant-negative recombinant herpes simplex virus type 1 (HSV-1) that is completely replication-defective, cannot establish detectable latent infection in vivo, and expresses high levels of the major HSV-1 antigen glycoprotein D immediately following infection. 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 [4,5,6,7]. 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]. HSV establishes latent infection in dorsal root ganglia with lifelong persistence, subsequently giving rise to intermittent reactivation and recurrent disease [9]. Considering the general impact of HSV-1 diseases and rising importance of primary genital herpes caused by HSV-1, a desirable vaccine should be capable of offering effective protective immunity against both HSV subtypes
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