A Live-Attenuated HSV-2 ICP0− Virus Elicits 10 to 100 Times Greater Protection against Genital Herpes than a Glycoprotein D Subunit Vaccine
Mice were treated with 2 mg medoxyprogesterone 7 and 3 days prior to vaginal HSV-2 challenge . On Days 80, 90, or 100 p.i., mice were challenged with 500,000 pfu per vagina of HSV-2 MS (n = 5 per group). The summated results from all three experiments are presented in each panel (∑n = 15 per group). (A) Vaginal HSV-2 shedding between Days 1 and 7 post-challenge in mice that were naïve or immunized with gD-21-306t versus HSV-2 0ΔNLS. (B) Vaginal HSV-2 shedding in mice that were naïve or immunized with GFP versus HSV-2 MS. In panels A and B, a single asterisk (*) denotes p<0.05 and a double asterisk (**) denotes p<0.001 that HSV-2 shedding was equivalent to naïve mice on that day, as determined by one-way ANOVA and Tukey's post hoc t-test. (C) Mean ± sem reduction in HSV-2 shedding on Days 1–7 post-challenge relative to the average titer of HSV-2 shed by naïve mice on that day (n = 75 per group). In panel C, a single asterisk (*) denotes p<0.05 and a double asterisk (**) denotes p<0.001 that reductions in vaginal shedding of HSV-2 MS were significantly greater than a value of 1, as determined by one-way ANOVA and Tukey's post hoc t-test. The difference in reductions in HSV-2 MS vaginal shedding between 0ΔNLS- and gD-2-immunized mice was significant (p<10−23; two-sided, paired t-test). (D) Survival frequency over time following HSV-2 MS challenge of the vagina. A double asterisk (**) denotes p<0.001 that survival frequency was equivalent to naïve mice, as determined by Fisher's Exact Test. The survival rate of gD-2 immunized mice was not significantly different than naïve mice (p = 0.22, Fisher's Exact Test).