A Live-Attenuated HSV-2 ICP0− Virus Elicits 10 to 100 Times Greater Protection against Genital Herpes than a Glycoprotein D Subunit Vaccine
Duration of survival following inoculation of naïve mice with culture medium containing 25,000 pfu per µl of (A) HSV-2 MS or (B) HSV-2 0ΔNLS following placement of 4 µl on left and right scarified eyes; 5 µl in left and right nostrils; 50 µl in left and right, rear footpads; or 20 µl instilled into the vaginal vault (n = 10 mice per group). A single asterisk (*) denotes a probability, p, <0.05 and a double asterisk (**) denotes p<0.001 that matched pairs of mice inoculated with (A) HSV-2 MS or (B) HSV-2 0ΔNLS survived at equivalent frequencies, as calculated by Fisher's Exact Test. (C) Mean ± sem abundance of gD-2 specific IgG antibody in mouse serum on Day 50 p.i., as determined by ELISA on 1∶100 dilutions of mouse serum (n = 10 per 0ΔNLS-immunization group; n = 5 MS-immunized mice). The y-axis represents relative units of IgG abundance expressed as “fold-increase above background,” as determined relative to a 0.33-log dilution series of high titer anti-HSV-2 antiserum that provided the standard curve that defined the quantitative relationship between anti-gD-2 IgG antibody abundance and the colorimetric development in each well of the ELISA plate (i.e., the standard curve had a goodness-of-fit of r2 = 0.99). A double asterisk (**) denotes a probability, p, <0.001 that gD-2-antibody levels were equivalent to naïve mice, as determined by one-way ANOVA and Tukey's post hoc t-test.