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 Wortmannin 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 MS-275 order 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 JSH-23 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 GNAT2 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.