Herpes simplex virus 2 ICP0- mutant viruses are avirulent and immunogenic: Implications for a genital herpes vaccine

Abstract

Herpes simplex virus 1 (HSV-1) ICP0- mutants are interferon-sensitive, avirulent, and elicit protective immunity against HSV- 1 (Virol J, 2006, 3:44). If an ICP0- mutant of herpes simplex virus 2 (HSV-2) exhibited similar properties, such a virus might be used to vaccinate against genital herpes. The current study was initiated to explore this possibility. Several HSV-2 ICP0- mutant viruses were constructed and evaluated in terms of three parameters: i. interferon-sensitivity; ii. virulence in mice; and iii. capacity to elicit protective immunity against HSV-2. One ICP0- mutant virus in particular, HSV-2 0DNLS, achieved an optimal balance between avirulence and immunogenicity. HSV-2 OΔNLS was interferon-sensitive in cultured cells. HSV-2 OΔNLS replicated to low levels in the eyes of inoculated mice, but was rapidly repressed by an innate, Stat 1-dependent host immune response. HSV-2 OΔNLS failed to spread from sites of inoculation, and hence produced only inapparent infections. Mice inoculated with HSV-2 OΔNLS consistently mounted an HSV-specific IgG antibody response, and were consistently protected against lethal challenge with wild-type HSV-2. Based on their avirulence and immunogenicity, we propose that HSV-2 ICP0- mutant viruses merit consideration for their potential to prevent the spread of HSV-2 and genital herpes. © 2010 Halford et al.