title: Antibodies Are Required for Complete Vaccine-Induced Protection against Herpes Simplex Virus 2.
abstract: Herpes simplex virus 2 (HSV-2) 0ΔNLS is a live HSV-2 ICP0- mutant vaccine strain that is profoundly attenuated in vivo due to its interferon-hypersensitivity. Recipients of the HSV-2 0ΔNLS vaccine are resistant to high-dose HSV-2 challenge as evidenced by profound reductions in challenge virus spread, shedding, disease and mortality. In the current study, we investigated the requirements for HSV-2 0ΔNLS vaccine-induced protection. Studies using (UV)-inactivated HSV-2 0ΔNLS revealed that self-limited replication of the attenuated virus was required for effective protection from vaginal or ocular HSV-2 challenge. Diminished antibody responses in recipients of the UV-killed HSV-2 vaccine suggested that antibodies might be playing a critical role in early protection. This hypothesis was investigated in B-cell-deficient μMT mice. Vaccination with live HSV-2 0ΔNLS induced equivalent CD8+ T cell responses in wild-type and μMT mice. Vaccinated μMT mice shed ~40-fold more infectious HSV-2 at 24 hours post-challenge relative to vaccinated wild-type (B-cell+) mice, and most vaccinated μMT mice eventually succumbed to a slowly progressing HSV-2 challenge. Importantly, passive transfer of HSV-2 antiserum restored full protection to HSV-2 0ΔNLS-vaccinated μMT mice. The results demonstrate that B cells are required for complete vaccine-induced protection against HSV-2, and indicate that virus-specific antibodies are the dominant mediators of early vaccine-induced protection against HSV-2.
authors.affiliation: Dept of Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, IL, 62702, United States of America.
authors.forename: William P
authors.initials: WP
authors.lastname: Halford
authors.affiliation: Dept of Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, IL, 62702, United States of America.
authors.forename: Joshua
authors.initials: J
authors.lastname: Geltz
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, 59840, United States of America.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Messer
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, 59840, United States of America.
authors.forename: Kim J
authors.initials: KJ
authors.lastname: Hasenkrug
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005123:Eye / Q000473:pathology; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006558:Herpes Genitalis / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000472:pathogenicity; D007106:Immune Sera / Q000276:immunology; D007114:Immunization; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D019913:Nuclear Localization Signals / Q000235:genetics; D014466:Ultraviolet Rays; D014621:Vagina / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D022301:Herpes Simplex Virus Vaccines; D007106:Immune Sera; D007074:Immunoglobulin G; D019913:Nuclear Localization Signals; D049452:Green Fluorescent Proteins