title: A Herpes Simplex Virus Type 1 Human Asymptomatic CD8+ T-Cell Epitopes-Based Vaccine Protects Against Ocular Herpes in a "Humanized" HLA Transgenic Rabbit Model.
abstract: OBJECTIVE
  A clinical vaccine that protects from ocular herpes simplex virus type 1 (HSV-1) infection and disease still is lacking. In the present study, preclinical vaccine trials of nine asymptomatic (ASYMP) peptides, selected from HSV-1 glycoproteins B (gB), and tegument proteins VP11/12 and VP13/14, were performed in the "humanized" HLA-transgenic rabbit (HLA-Tg rabbit) model of ocular herpes. We recently reported that these peptides are highly recognized by CD8+ T cells from "naturally" protected HSV-1-seropositive healthy ASYMP individuals (who have never had clinical herpes disease).
  
  
  METHODS
  Mixtures of three ASYMP CD8+ T-cell peptides derived from either HSV-1 gB, VP11/12, or VP13/14 were delivered subcutaneously to different groups of HLA-Tg rabbits (n = 10) in incomplete Freund's adjuvant, twice at 15-day intervals. The frequency and function of HSV-1 epitope-specific CD8+ T cells induced by these peptides and their protective efficacy, in terms of survival, virus replication in the eye, and ocular herpetic disease were assessed after an ocular challenge with HSV-1 (strain McKrae).
  
  
  RESULTS
  All mixtures elicited strong and polyfunctional IFN-γ- and TNF-α-producing CD107+CD8+ cytotoxic T cells, associated with a significant reduction in death, ocular herpes infection, and disease (P < 0.015).
  
  
  CONCLUSIONS
  The results of this preclinical trial support the screening strategy used to select the HSV-1 ASYMP CD8+ T-cell epitopes, emphasize their valuable immunogenic and protective efficacy against ocular herpes, and provide a prototype vaccine formulation that may be highly efficacious for preventing ocular herpes in humans.
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, United States.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Srivastava
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, United States.
authors.forename: Arif A
authors.initials: AA
authors.lastname: Khan
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, United States.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Huang
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, United States.
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Nesburn
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, United States 2Department of Microbiology and Molecular Genetics, University of California Irvine, Schoo.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wechsler
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, California, United States 4Department of Molecular Biology & Biochemistry 5Institute for Immunology, University of C.
authors.forename: Lbachir
authors.initials: L
authors.lastname: BenMohamed
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000276:immunology; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000379:methods*; D016849:Keratitis, Herpetic / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D022301:Herpes Simplex Virus Vaccines; D014409:Tumor Necrosis Factor-alpha