title: Zoster Vaccination Increases the Breadth of CD4+ T Cells Responsive to Varicella Zoster Virus.
abstract: BACKGROUND
  The live, attenuated varicella vaccine strain (vOka) is the only licensed therapeutic vaccine. Boost of varicella zoster virus (VZV)-specific cellular immunity is a likely mechanism of action. We examined memory CD4(+) T-cell responses to each VZV protein at baseline and after zoster vaccination.
  
  
  METHODS
  Serial blood samples were collected from 12 subjects vaccinated with Zostavax and immunogenicity confirmed by ex vivo VZV-specific T-cell and antibody assays. CD4(+) T-cell lines enriched for VZV specificity were generated and probed for proliferative responses to every VZV protein and selected peptide sets.
  
  
  RESULTS
  Zoster vaccination increased the median magnitude (2.3-fold) and breadth (4.2-fold) of VZV-specific CD4(+) T cells one month post-vaccination. Both measures declined by 6 months. The most prevalent responses at baseline included VZV open reading frames (ORFs) 68, 4, 37, and 63. After vaccination, responses to ORFs 40, 67, 9, 59, 12, 62, and 18 were also prevalent. The immunogenicity of ORF9 and ORF18 were confirmed using peptides, defining a large number of discrete CD4 T-cell epitopes.
  
  
  CONCLUSIONS
  The breadth and magnitude of the VZV-specific CD4(+) T-cell response increase after zoster vaccination. In addition to glycoprotein E (ORF68), we identified antigenic ORFs that may be useful components of subunit vaccines.
authors.affiliation: Department of Medicine, University of Washington, Seattle.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Laing
authors.affiliation: Department of Medicine, University of Washington, Seattle.
authors.forename: Ronnie M
authors.initials: RM
authors.lastname: Russell
authors.affiliation: Department of Medicine, University of Washington, Seattle.
authors.forename: Lichun
authors.initials: L
authors.lastname: Dong
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: D Scott
authors.initials: DS
authors.lastname: Schmid
authors.affiliation: Department of Laboratory Medicine.
authors.forename: Michael
authors.initials: M
authors.lastname: Stern
authors.affiliation: Department of Laboratory Medicine Department of Biostatistics, University of Washington Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Amalia
authors.initials: A
authors.lastname: Magaret
authors.affiliation: Division of Infection and Pathway Medicine, University of Edinburgh, United Kingdom.
authors.forename: Jürgen G
authors.initials: JG
authors.lastname: Haas
authors.affiliation: Department of Medicine, University of Washington, Seattle Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Christine
authors.initials: C
authors.lastname: Johnston
authors.affiliation: Department of Medicine, University of Washington, Seattle Department of Laboratory Medicine Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington Department of Epidemiology.
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.affiliation: Department of Medicine, University of Washington, Seattle Department of Laboratory Medicine Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington Department of Global Health, University of Washington Benaroya Research Institute, Seattle, Washington.
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006562:Herpes Zoster / Q000276:immunology* / Q000517:prevention & control; D053061:Herpes Zoster Vaccine / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008875:Middle Aged; D008969:Molecular Sequence Data; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D053061:Herpes Zoster Vaccine; D014613:Vaccines, Attenuated
keywords: T lymphocytes; epitopes; vaccine; varicella zoster virus