title: Safety and immunogenicity of an adjuvanted herpes zoster subunit candidate vaccine in HIV-infected adults: a phase 1/2a randomized, placebo-controlled study.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV)-infected individuals are at increased risk of herpes zoster (HZ), even in the antiretroviral therapy (ART) era. Because concerns exist about the use of live-attenuated vaccines in immunocompromised individuals, a subunit vaccine may be an appropriate alternative.
  
  
  METHODS
  This phase 1/2, randomized, placebo-controlled study evaluated the immunogenicity and safety of an investigational HZ subunit vaccine (HZ/su). Three cohorts of HIV-infected adults aged ≥18 years were enrolled: 94 ART recipients with a CD4(+) T-cell count of ≥200 cells/mm(3), 14 ART recipients with a CD4(+) T-cell count of 50-199 cells/mm(3), and 15 ART-naive adults with a CD4(+) T-cell count of ≥500 cells/mm(3). Subjects received 3 doses of HZ/su (50 µg varicella-zoster virus glycoprotein E [gE] combined with AS01B adjuvant) or 3 doses of saline at months 0, 2, and 6.
  
  
  RESULTS
  One month after dose 3, serum anti-gE antibody concentrations and frequencies of gE-specific CD4(+) T cells were higher following HZ/su vaccination than after receipt of saline (P < .0001). Median cell-mediated immune responses peaked after dose 2. Humoral and cell-mediated immune responses persisted until the end of the study (month 18). No vaccination-related serious adverse events were reported. No sustained impact on HIV load or CD4(+) T-cell count was noted following vaccinations.
  
  
  CONCLUSIONS
  HZ/su was immunogenic and had a clinically acceptable safety profile in HIV-infected adults.
  
  
  BACKGROUND
  NCT01165203.
authors.affiliation: GlaxoSmithKline Vaccines, King of Prussia, Pennsylvania.
authors.forename: Elchonon M
authors.initials: EM
authors.lastname: Berkowitz
authors.affiliation: Chelsea and Westminster Hospital.
authors.forename: Graeme
authors.initials: G
authors.lastname: Moyle
authors.affiliation: Infektionsmedizinisches Centrum Hamburg.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Stellbrink
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schürmann
authors.affiliation: Queen Elizabeth Hospital NHS Trust, The Trafalgar Clinic, London, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kegg
authors.affiliation: Medizinische Hochschule Hannover, Zentrum Innere Medizin, Klinische Immunologie II, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Stoll
authors.affiliation: GlaxoSmithKline Vaccines, Wavre, Belgium.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Idrissi
authors.affiliation: GlaxoSmithKline Vaccines, Wavre, Belgium.
authors.forename: Lidia
authors.initials: L
authors.lastname: Oostvogels
authors.affiliation: GlaxoSmithKline Vaccines, King of Prussia, Pennsylvania.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Heineman
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006562:Herpes Zoster / Q000276:immunology*; D053061:Herpes Zoster Vaccine / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; D000914:Antibodies, Viral; D053061:Herpes Zoster Vaccine; D022223:Vaccines, Subunit
keywords: HIV infection; glycoprotein E; herpes zoster; immunodeficiency; varicella-zoster virus; zoster vaccine