Duration of protection from live attenuated vs. sub unit HSV-2 vaccines in the guinea pig model of genital herpes: Reassessing efficacy using endpoints from clinical trials

Abstract
Background
Although herpes simplex viruses (HSV) are a major target for vaccine development no vaccine is currently licensed.

Methods
A live attenuated HSV virus vaccine, VC2 was compared to a subunit HSV vaccine, glycoprotein D (gD2) administered with the adjuvant, MPL/Alum using the guinea pig model of genital herpes. Three doses of intramuscular (IM) vaccine were provided followed by intra-vaginal challenge with HSV-2 at either 3 weeks or six months after the last vaccination.

Results
Both VC2 and gD2 vaccines reduced acute genital disease. VC2 was somewhat more effective in reducing acute vaginal replication, the amount of virus in neural tissue, subsequent recurrent disease and recurrent virus shedding following challenge at 3 weeks post vaccination. Both vaccines continued to provide protection at 6 months after vaccination but the differences between the vaccines became more pronounced in favor of the live attenuated vaccine, VC2. Significant differences in acute disease, acute vaginal virus replication, recurrent disease and recurrent virus shedding (P