Abstract
Treatment to ameliorate the symptoms of infection with herpes simplex virus 2 (HSV-2) and to suppress reactivation has been available for decades. However, a safe and effective preventative or therapeutic vaccine has eluded development. Two novel live-attenuated HSV-2 vaccine candidates (RVx201 and RVx202) have been tested preclinically for safety. Hartley guinea pigs were inoculated vaginally (n = 3) or intradermally (n = 16) with either vaccine candidate (2 × 107 PFU) and observed for disease for 28 days. All animals survived to study end without developing HSV-2-associated disease. Neither vaccine candidate established latency in dorsal root or sacral sympathetic ganglia, as determined by viral DNA quantification, LAT expression, or explant reactivation. Infectious virus was shed in vaginal secretions for three days following vaginal inoculation with RVx202, but not RVx201, although active or latent HSV-2 was not detected at study end. In contrast, guinea pigs inoculated with wild-type HSV-2 MS (2 × 105 PFU) vaginally (n = 5) or intradermally (n = 16) developed acute disease, neurological signs, shed virus in vaginal secretions, experienced periodic recurrences throughout the study period, and had latent HSV-2 in their dorsal root and sacral sympathetic ganglia at study end. Both vaccine candidates generated neutralizing antibody. Taken together, these findings suggest that these novel vaccine candidates are safe in guinea pigs and should be tested for efficacy as preventative and/or therapeutic anti-HSV-2 vaccines.
Highlights
Introduction published maps and institutional affilherpes simplex virus 2 (HSV-2) remains the leading cause of genital herpes and is associated with 60% of genital ulcers in the United States, Asia, Africa, and parts of Europe [1]
As an initial goal is to assess the vaccine candidates as potential therapeutics to prevent recurrent disease in individuals who are already infected with HSV-2, we sought to assess the safety of the vaccine candidates in the guinea pig model
Mice prevented infection after challenge with wild type (WT) HSV-2 [95]. These results suggest that attenuated HSV-2 vaccine candidates may be able to generate a more Th1 biased response targeting destruction of HSV-2 infected cells rather than the more Th2 biased response generated by WT HSV-2 infection, which has been indicated as a factor limiting the efficacious destruction of HSV-2-infected cells
Summary
Introduction published maps and institutional affilHSV-2 remains the leading cause of genital herpes and is associated with 60% of genital ulcers in the United States, Asia, Africa, and parts of Europe [1]. The epidemiology of genital herpes is changing, as first-time genital herpes infections in industrialized, high income countries are increasingly associated with HSV-1, especially among individuals under 25 years of age, college students, females, and men who have sex with men. This is likely driven by reduced prevalence of early childhood HSV-1 infection, leaving adolescents and young-adults susceptible to genital infection when they become sexually active [1,2,3,4].
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