title: Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.
abstract: Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden.
authors.forename: Josefine
authors.initials: J
authors.lastname: Persson
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden.
authors.forename: Thorunn A
authors.initials: TA
authors.lastname: Olafsdottir
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden.
authors.forename: Karolina
authors.initials: K
authors.lastname: Thörn
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania , Philadelphia, PA , USA.
authors.forename: Tina M
authors.initials: TM
authors.lastname: Cairns
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford , Oxford , UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Wegmann
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford , Oxford , UK.
authors.forename: Quentin J
authors.initials: QJ
authors.lastname: Sattentau
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA , USA.
authors.forename: Roselyn J
authors.initials: RJ
authors.lastname: Eisenberg
authors.affiliation: Department of Microbiology, School of Dental Medicine, University of Pennsylvania , Philadelphia, PA , USA.
authors.forename: Gary H
authors.initials: GH
authors.lastname: Cohen
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden.
authors.forename: Ali M
authors.initials: AM
authors.lastname: Harandi
keywords: competitive surface plasmon resonance assay; genital herpes; nasal immunization; neutralizing antibody; sexually transmitted infection, vaccine