This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Both HSV -1 and HSV -2 can cause primary infection of the genital tract. However, cases of genital HSV are caused by HSV -2. In the USA HSV-2 seroprevalence has risen sharply during the past 20 years, with a current mean seroprevalence of 22% [1}. HSV-2 infection occurs worldwide and appears epidemic in some populations [2]. Among seropositive individuals, 20-50% experience episodes of symptomatic genital herpes disease, [3,4]. Symptomatic disease may be severe, with painful vesiculo-ulcerative skin lesions, and complications such as urinary retention and meningitis [5,6]. Patients diagnosed genital herpes undergo physical and psychological suffering that can significantly affect their quality of life [7,8,9]. While there is no cure for genital herpes at this time, strategies to control genital herpes infection and disease have mainly focused on antiviral chemotberapy, education, and the use of condoms. The evidence suggests that only the widespread use of an effective vaccine may be helpful in controlling genital herpes. Methods: GSK Biologicals has developed a candidate herpes vaccine that has been evaluated in two phase III efficacy studies [12,13}. The candidate vaccine is a HSV-2 glycoprotein D (gD2t) subunit vaccine adjuvanted with alum combined with 3-deacylated monophosphoryl lipid A (MPL). Preliminary Results: Efficacy data from these two Phase III studies are now available [studies208141/005 (HSV-007) and 208141/017 (HSV-017)]. In study HSV-007, statistically significant vaccine efficacy against the acquisition of genital herpes disease in the overall cohort of HSV -1/-2 subjects was not observed (months 0-19 intention-to-treat cohort [ITT]: vaccine efficacy [VE] == 38%; 95% CI: -17, 67; p= 0.14); months 2-19 according-to-protocol [ATP] cohort: VE == 25%; 95% CI: -56, 64; p = 0.45). Logistic regression analysis indicated a statistically significant gender-by-group interaction for the efficacy analysis in the ITT cohort (p=0.035). Evaluation of the ITT cohort by gender using attack rate analyses indicated vaccine efficacy against genital herpes disease in females (VE= 73%; 95% CI: = 19,91, p= 0.01). In study HSV -017, statistically significant vaccine efficacy against the acquisition of genital herpes disease in HSV-2 seronegative females (primary efficacy endpoint) was not observed (month 0-19 ITT cohort: VE == 42%; 95% CL: -31, 74; p = 0.18); month 2-19 ATP cohort: VE = 43%; 95% CI: -29, 75; p = 0.17). However, separate analysis of HSV 1 -/2- females indicated significant efficacy (ITT cohort: VE = 74%; 95% C.I.: 9,93; p = 0.02; ATP cohort: VE = 73.1 %; 95% CI.: 5,92; p = 0.03). There was no evidence of vaccine efficacy in HSV-2 seronegative males (ITT cohort: VE = -10%; 95% CI: -127, 47; p = 0.80). Conclusion: In summary, both trials demonstrated vaccine efficacy against acquisition of genital herpes disease in HSV 1-/2- women. These efficacy data suggest the possibility of preventing a disease of significant public health importance in women.
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