title: Long-term immunogenicity and safety of an investigational herpes zoster subunit vaccine in older adults.
abstract: BACKGROUND
  An investigational subunit vaccine containing the varicella-zoster virus (VZV) glycoprotein E (gE) and the AS01B adjuvant system is being evaluated for the prevention of herpes zoster (HZ) in older adults. A phase II trial evaluating different formulations of this vaccine (containing 25μg, 50μg, or 100μg gE) was conducted in adults ≥60 years of age and showed that all formulations elicited robust cellular and humoral immune responses for up to 3 years after vaccination. In this follow-up study in subjects who received two doses of the 50μg gE/AS01B formulation (HZ/su), we assessed the persistence of the immune responses for up to 6 years after vaccination.
  
  
  METHODS
  This phase II, open-label, multicenter, single-group trial conducted in the Czech Republic, Germany, Sweden, and the Netherlands followed 129 subjects who had received two doses (2 months apart) of HZ/su during the initial trial. Vaccine-induced immune responses (frequencies of gE-specific CD4(+) T cells expressing ≥2 activation markers and serum anti-gE antibody concentrations) were evaluated at 48, 60, and 72 months after the first HZ/su dose.
  
  
  RESULTS
  Six years after vaccination with HZ/su, gE-specific cell-mediated immune responses and anti-gE antibody concentrations had decreased by 20-25% from month 36, but remained higher than the prevaccination values. At month 72, the gE-specific cell-mediated immune response was 3.8 times higher than the prevaccination value (477.3 vs. 119.4 activated gE-specific CD4(+) T cells per 10(6) cells), and the anti-gE antibody concentration was 7.3 times higher than the prevaccination value (8159.0 vs. 1121.3mIU/mL). No vaccine-related serious adverse events were reported between months 36 and 72.
  
  
  CONCLUSIONS
  gE-specific cellular and humoral immune responses persisted for 6 years after two-dose vaccination with HZ/su in healthy older adults. No safety concerns were identified.
authors.affiliation: Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Chlibek
authors.affiliation: Department of Medical Science, Section of Infectious Diseases Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden.
authors.forename: Karlis
authors.initials: K
authors.lastname: Pauksens
authors.affiliation: Clinical Research Center, Sormland County Council, Uppsala University, Eskilstuna, Sweden; Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Rombo
authors.affiliation: Public Health Service Amsterdam, Department of Infectious Diseases, Amsterdam, The Netherlands.
authors.forename: Gini
authors.initials: G
authors.lastname: van Rijckevorsel
authors.affiliation: Municipal Public Health Service Rotterdam-Rijnmond, Rotterdam, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Richardus
authors.affiliation: Unterfrintroper Hausarztzentrum, Essen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Plassmann
authors.affiliation: Central Laboratory and Vaccination Centre, Stiftung Juliusspital, Würzburg, Germany.
authors.forename: Tino F
authors.initials: TF
authors.lastname: Schwarz
authors.affiliation: GSK Vaccines, Wavre, Belgium.
authors.forename: Grégory
authors.initials: G
authors.lastname: Catteau
authors.affiliation: GSK Vaccines, King of Prussia, PA, USA. Electronic address: himal.x.lal@gsk.com.
authors.forename: Himal
authors.initials: H
authors.lastname: Lal
authors.affiliation: GSK Vaccines, King of Prussia, PA, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Heineman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006562:Herpes Zoster / Q000517:prevention & control*; D053061:Herpes Zoster Vaccine / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D012503:Saponins / Q000008:administration & dosage; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use*; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D004338:Drug Combinations; D053061:Herpes Zoster Vaccine; D008050:Lipid A; D012503:Saponins; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C000592464:adjuvant system 01
keywords: Glycoprotein E; Immunogenicity; NCT01295320; Persistence; Subunit vaccine; Varicella-zoster virus