A recent study showed that the replication-defective HSV-2 recombinant dl5-29 was more effective than the HSV-2-gD-based subunit vaccine in inducing HSV-2-specific neutralizing antibodies and CD8+ T-cell response in mice [43]. CJ9-gD is an HSV-1 recombinant defective at level of viral DNA replication, and therefore, similar to dl5-29, capable of expressing a broad spectrum of viral antigens. In addition, it has a unique dominant-negative effect on viral replication (UL9-C535C expression) and

expresses high levels of the major HSV-1 antigen gD at the immediate-early phase of infection [27]. Immunization with CJ9-gD led to 220-fold reduction in the yield of challenge wild-type HSV-2 in genital swabs materials on day 2 post-challenge R788 in vitro compared with mock-immunized controls. Noting that immunization with gD2/AS04 resulted in less than 14-fold challenge wild-type HSV-2 (strain

MS) viral replication compared with mock-immunized controls PD0325901 manufacturer on day 2 post-challenge, and all mock-immunized animals survived after recovery from primary disease caused by challenge virus [20], our study suggests that CJ9-gD could potentially be more efficacious than gD2 subunit vaccine against HSV-2 genital disease. It will be interesting to test the vaccine efficacy of gD2/AS04 and CJ9-gD in protecting against HSV-2 genital herpes in the same experimental settings. Moreover, in light of that CJ9-gD expresses high-level of gD, and induction of both effective mucosal and systemic immune responses is likely required for an optimal protection against HSV genital infection, it would be of great interest to investigate the effectiveness of CJ9-gD in induction of humoral and T-cell immunity following different routes of immunization and whether the efficacy of CJ9-gD in eliciting mucosal immune response can be enhanced by gD subunit prime/CJ9-gD boost regimen involving combination of mucosal and systemic immunization

[44–46]. Many type-common and type-specific antibodies as well as T cell epitopes have been identified against various HSV-1 and HSV-2 proteins. Mice immunized with CJ9-gD develop Atazanavir stronger humoral and cellular immune responses against HSV-1 than against HSV-2, and are significantly better protected against genital infection with HSV-1 than with HSV-2 [29]. These findings are in agreement with the previous reports that in rodents HSV vaccines are generally less effective in prevention of heterotypic HSV infection than homotypic infection [47, 48]. Combined with observations that humans who were previously infected with HSV-2 are less likely to experience re-infection with a heterologous strain of HSV-2 than individuals with prior HSV-1 infection [49–53], it is reasonable to believe, that a CJ9-gD-like dominant-negative HSV-2 recombinant would be more effective in prevention of genital HSV-2 infection than the HSV-1 recombinant CJ9-gD.