Liposomal gD ectodomain (gD 1–306) vaccine protects against HSV2 genital or rectal infection of female and male mice

Abstract

Herpes simplex virus type 2 (HSV2) is the most common causative agent of genital herpes, with infection rates as high as 1 in 6 adults. The present studies were done to evaluate the efficacy of a liposomal HSV2 gD 1–306 vaccine (L-gD 1–306-HD) in an acute murine HSV2 infection model of intravaginal (female) or intrarectal (male or female) challenge. Two doses of L-gD 1–306-HD containing 60 μg gD 1–306-HD and 15 μg monophosphoryl lipid A (MPL) per dose provided protection against HSV2 intravaginal challenge (86–100% survival, P ≤ 0.0003 vs. control liposomes; P = 0.06 vs. L-gD 1–306-HD without MPL). Both male and female mice (BALB/c and C57BL/6) immunized with L-gD 1–306-HD/MPL were significantly protected against HSV2 intrarectal challenge, with higher survival rates compared to controls (71–100%, P ≤ 0.007). L-gD 1–306-HD/MPL also provided increased survival when compared to a liposomal peptide vaccine, L-gD 264–285-HD/MPL (male BALB/c, P ≤ 0.001; female BALB/c and male C57BL/6, P = 0.06). Mice given L-gD 1–306-HD/MPL also had minimal disease signs, reduced viral burden in their spinal cords and elevated neutralizing antibody titers in the females. The vaccine also stimulated gD 1–306-HD specific splenocytes of both male and female mice with significantly elevated levels of IFN-γ compared to IL-4 ( P ≤ 0.01) indicating that there was an enhanced Th1 response. These results provide the first evidence that the L-gD 1–306-HD vaccine can protect both male and female mice against intrarectal HSV2 challenge.