title: An HSV-2 Trivalent Vaccine Is Immunogenic in Rhesus Macaques and Highly Efficacious in Guinea Pigs.
abstract: 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.
authors.affiliation: Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Sita
authors.identifier: 0000-0001-8230-3635
authors.initials: S
authors.lastname: Awasthi
authors.affiliation: Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Hook
authors.affiliation: Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Carolyn E
authors.initials: CE
authors.lastname: Shaw
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, United States of America.
authors.forename: Bapi
authors.initials: B
authors.lastname: Pahar
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, United States of America.
authors.forename: Jacob A
authors.identifier: 0000-0002-1764-1096
authors.initials: JA
authors.lastname: Stagray
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Liu
authors.affiliation: Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, United States of America.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
authors.affiliation: Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Harvey M
authors.identifier: 0000-0002-0765-9460
authors.initials: HM
authors.lastname: Friedman
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006168:Guinea Pigs; D006561:Herpes Simplex / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008253:Macaca mulatta; D016133:Polymerase Chain Reaction; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D022283:Herpesvirus Vaccines; D022223:Vaccines, Subunit