title: Protection provided by a herpes simplex virus 2 (HSV-2) glycoprotein C and D subunit antigen vaccine against genital HSV-2 infection in HSV-1-seropositive guinea pigs.
abstract: A prophylactic vaccine for genital herpes disease remains an elusive goal. We report the results of two studies performed collaboratively in different laboratories that assessed immunogenicity and vaccine efficacy in herpes simplex virus 1 (HSV-1)-seropositive guinea pigs immunized and subsequently challenged intravaginally with HSV-2. In study 1, HSV-2 glycoproteins C (gC2) and D (gD2) were produced in baculovirus and administered intramuscularly as monovalent or bivalent vaccines with CpG and alum. In study 2, gD2 was produced in CHO cells and given intramuscularly with monophosphoryl lipid A (MPL) and alum, or gC2 and gD2 were produced in glycoengineered Pichia pastoris and administered intramuscularly as a bivalent vaccine with Iscomatrix and alum to HSV-1-naive or -seropositive guinea pigs. In both studies, immunization boosted neutralizing antibody responses to HSV-1 and HSV-2. In study 1, immunization with gC2, gD2, or both immunogens significantly reduced the frequency of genital lesions, with the bivalent vaccine showing the greatest protection. In study 2, both vaccines were highly protective against genital disease in naive and HSV-1-seropositive animals. Comparisons between gD2 and gC2/gD2 in study 2 must be interpreted cautiously, because different adjuvants, gD2 doses, and antigen production methods were used; however, significant differences invariably favored the bivalent vaccine. Immunization of naive animals with gC2/gD2 significantly reduced the number of days of vaginal shedding of HSV-2 DNA compared with that for mock-immunized animals. Surprisingly, in both studies, immunization of HSV-1-seropositive animals had little effect on recurrent vaginal shedding of HSV-2 DNA, despite significantly reducing genital disease.
authors.affiliation: Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Sita
authors.initials: S
authors.lastname: Awasthi
authors.forename: John W
authors.initials: JW
authors.lastname: Balliet
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Flynn
authors.forename: John M
authors.initials: JM
authors.lastname: Lubinski
authors.forename: Carolyn E
authors.initials: CE
authors.lastname: Shaw
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DiStefano
authors.forename: Michael
authors.initials: M
authors.lastname: Cai
authors.forename: Martha
authors.initials: M
authors.lastname: Brown
authors.forename: Judith F
authors.initials: JF
authors.lastname: Smith
authors.forename: Rose
authors.initials: R
authors.lastname: Kowalski
authors.forename: Ryan
authors.initials: R
authors.lastname: Swoyer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Galli
authors.forename: Victoria
authors.initials: V
authors.lastname: Copeland
authors.forename: Sandra
authors.initials: S
authors.lastname: Rios
authors.forename: Robert C
authors.initials: RC
authors.lastname: Davidson
authors.forename: Maya
authors.initials: M
authors.lastname: Salnikova
authors.forename: Susan
authors.initials: S
authors.lastname: Kingsley
authors.forename: Janine
authors.initials: J
authors.lastname: Bryan
authors.forename: Danilo R
authors.initials: DR
authors.lastname: Casimiro
authors.forename: Harvey M
authors.initials: HM
authors.lastname: Friedman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D016367:Baculoviridae; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000517:prevention & control*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007273:Injections, Intramuscular; D008050:Lipid A / Q000031:analogs & derivatives; D010843:Pichia; D060888:Real-Time Polymerase Chain Reaction; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D057134:Antibodies, Neutralizing; D008050:Lipid A; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C048232:glycoprotein C, herpes simplex virus type 2; C040570:glycoprotein D-herpes simplex virus type 2; C048436:monophosphoryl lipid A