title: Therapeutic vaccination expands and improves the function of the HIV-specific memory T-cell repertoire.
abstract: BACKGROUND
  The licensing of herpes zoster vaccine has demonstrated that therapeutic vaccination can help control chronic viral infection. Unfortunately, human trials of immunodeficiency virus (HIV) vaccine have shown only marginal efficacy.
  
  
  METHODS
  In this double-blind study, 17 HIV-infected individuals with viral loads of <50 copies/mL and CD4(+) T-cell counts of >350 cells/µL were randomly assigned to the vaccine or placebo arm. Vaccine recipients received 3 intramuscular injections of HIV DNA (4 mg) coding for clade B Gag, Pol, and Nef and clade A, B, and C Env, followed by a replication-deficient adenovirus type 5 boost (10(10) particle units) encoding all DNA vaccine antigens except Nef. Humoral, total T-cell, and CD8(+) cytotoxic T-lymphocyte (CTL) responses were studied before and after vaccination. Single-copy viral loads and frequencies of latently infected CD4(+) T cells were determined.
  
  
  RESULTS
  Vaccination was safe and well tolerated. Significantly stronger HIV-specific T-cell responses against Gag, Pol, and Env, with increased polyfunctionality and a broadened epitope-specific CTL repertoire, were observed after vaccination. No changes in single-copy viral load or the frequency of latent infection were observed.
  
  
  CONCLUSIONS
  Vaccination of individuals with existing HIV-specific immunity improved the magnitude, breadth, and polyfunctionality of HIV-specific memory T-cell responses but did not impact markers of viral control.
  
  
  BACKGROUND
  NCT00270465.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH),Bethesda, Maryland 20892, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Casazza
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Bowman
authors.forename: Selorm
authors.initials: S
authors.lastname: Adzaku
authors.forename: Emily C
authors.initials: EC
authors.lastname: Smith
authors.forename: Mary E
authors.initials: ME
authors.lastname: Enama
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.forename: Ingelise J
authors.initials: IJ
authors.lastname: Gordon
authors.forename: David R
authors.initials: DR
authors.lastname: Ambrozak
authors.forename: Martha C
authors.initials: MC
authors.lastname: Nason
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Charla A
authors.initials: CA
authors.lastname: Andrews
authors.forename: Frank M
authors.initials: FM
authors.lastname: Maldarelli
authors.forename: Ann
authors.initials: A
authors.lastname: Wiegand
authors.forename: Mary F
authors.initials: MF
authors.lastname: Kearney
authors.forename: Deborah
authors.initials: D
authors.lastname: Persaud
authors.forename: Carrie
authors.initials: C
authors.lastname: Ziemniak
authors.forename: Raphael
authors.initials: R
authors.lastname: Gottardo
authors.forename: Julie E
authors.initials: JE
authors.lastname: Ledgerwood
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004311:Double-Blind Method; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005500:Follow-Up Studies; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology; D006801:Humans; D056724:Immunity, Humoral; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D019562:Viral Load; D017735:Virus Latency
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D011994:Recombinant Proteins
keywords: HIV; cytotoxic T lymphocytes; humoral immunity; therapy; vaccination; viral latency