title: Durable HIV-1 antibody and T-cell responses elicited by an adjuvanted multi-protein recombinant vaccine in uninfected human volunteers.
abstract: BACKGROUND
  Use of the recombinant proteins NefTat and gp120(W61D) formulated with the AS02A adjuvant system was previously shown to protect against AIDS in a rhesus macaque SHIV animal model system.
  
  
  METHODS
  Eighty-four HIV uninfected human participants were vaccinated intramuscularly at 0, 1, and 3 months and evaluated for safety. Immune responses were analyzed for the presence of vaccine-induced antibody and T lymphocyte responses.
  
  
  RESULTS
  The vaccines were safe and well tolerated at all doses. Nef-, Tat-, and gp120-specific binding antibodies were induced in all individuals that received the respective antigen, lasting up to 9 months after the final immunization. Antibodies able to neutralize the T-cell laboratory-adapted strain of HIV-1(W61D) were detected in the majority of vacinees, but did not neutralize primary isolates. Envelope-specific antibody-dependent cell cytoxicity was detected in most of the individuals receiving gp120. Robust and persistent HIV-specific lymphoproliferative responses were detected against all subunit proteins in the majority of immunized participants. As expected, HIV-specific CD8 T-cell responses were not detected.
  
  
  CONCLUSIONS
  Despite the lack of primary isolate neutralizing antibody induction, the observed high frequency and magnitude of other immune responses warrant further work with this vaccine or vaccine components.
authors.affiliation: University of Alabama at Birmingham, 908 20th Street South, CCB 328, Birmingham, AL 35294, USA. paulg@uab.edu
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Helen
authors.initials: H
authors.lastname: Horton
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Mark
authors.initials: M
authors.lastname: Deers
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
authors.forename: Marguerite
authors.initials: M
authors.lastname: Koutsoukos
authors.forename: Louise
authors.initials: L
authors.lastname: Pedneault
authors.forename: Pierre
authors.initials: P
authors.lastname: Vandepapeliere
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Paul
authors.initials: P
authors.lastname: Spearman
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Fuchs
authors.forename: Beryl A
authors.initials: BA
authors.lastname: Koblin
authors.forename: William A
authors.initials: WA
authors.lastname: Blattner
authors.forename: Sharon
authors.initials: S
authors.lastname: Frey
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: Clayton
authors.initials: C
authors.lastname: Harro
authors.forename: Thomas
authors.initials: T
authors.lastname: Evans
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000917:Antibody Formation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000009:adverse effects / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis; D017780:Malaria Vaccines / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D017780:Malaria Vaccines; C493155:RTS,S-AS02A vaccine; D014614:Vaccines, Synthetic; D007371:Interferon-gamma