A
genital herpes vaccine is urgently needed to prevent
pain and suffering, reduce the incidence of
neonatal herpes, and decrease the risk of HIV acquisition and transmission that accompanies genital
infection. We evaluated a trivalent HSV-2 subunit
antigen vaccine administered with CpG and
alum in rhesus macaques and guinea pigs. The
vaccine contains
glycoproteins C, D and E (gC2, gD2, gE2) to block virus entry by gD2 and immune evasion by gC2 and gE2. In rhesus macaques, the trivalent
vaccine induced plasma and mucosa
neutralizing antibodies,
antibodies that block gC2 and gE2 immune evasion activities, and stimulated CD4 T cell responses. After intravaginal challenge, a self-limited vaginal
infection of brief duration was detected by histopathology and immunohistochemistry in naïve, but not in trivalent immunized macaques.
Vaccine efficacy was evaluated in female guinea pigs. Animals were mock immunized, or immunized with gD2, the trivalent
vaccine or the trivalent
vaccine followed by a booster dose of gD2 (trivalent + gD2). The trivalent and trivalent + gD2 groups were 97% and 99% efficacious, respectively in preventing genital lesions and both outperformed gD2 alone. As a marker of transmission risk, vaginal swabs were evaluated daily for HSV-2
DNA and replication competent virus between five and seven weeks after challenge. HSV-2
DNA shedding was reduced in all groups compared with mock. Shedding of replication competent virus occurred on fewer days in the trivalent than gD2 immunized animals while the trivalent + gD2 group had no shedding of replication competent virus. Overall, the trivalent group had genital lesions on < 1% days and shedding of replication competent virus on 0.2% days. The
vaccine has outstanding potential for prevention of
genital herpes in humans.