title: Induction of strong HIV-1-specific CD4+ T-cell responses using an HIV-1 gp120/NefTat vaccine adjuvanted with AS02A in antiretroviral-treated HIV-1-infected individuals.
abstract: BACKGROUND
  Induction of HIV-1-specific CD4(+) T-cell responses by therapeutic vaccination represents an attractive intervention to potentially increase immune control of HIV-1.
  
  
  METHODS
  We performed a double-blinded, randomized, placebo-controlled clinical trial to determine the safety and immunogenicity of GlaxoSmithKline Biologicals' HIV-1 gp120/NefTat subunit protein vaccine formulated with the AS02(A) Adjuvant System in subjects with well-controlled chronic HIV-1 infection on highly active antiretroviral therapy. Ten individuals received the vaccine; whereas adjuvant alone or placebo was given to 5 subjects each. Immunogenicity was monitored by intracellular cytokine flow cytometry and carboxyfluorescein succinimidyl ester-based proliferation assays.
  
  
  RESULTS
  The vaccine was well tolerated with no related serious adverse events. Vaccine recipients had significantly stronger gp120-specific CD4(+) T-cell responses which persisted until week 48 and greater gp120-specific CD4(+) T-cell proliferation activity as compared with controls. In the vaccine group, the number of participants who demonstrated positive responses for both gp120-specific CD4(+) T-cell interleukin-2 production and gp120-specific CD8(+) T-cell proliferation were significantly higher at week 6.
  
  
  CONCLUSIONS
  The gp120/NefTat/AS02(A) vaccine induced strong gp120-specific CD4(+) T-cell responses and a higher number of vaccinees developed both HIV-1-specific CD4(+) T-cell responses and CD8(+) T-cell proliferation. The induction of these responses may be important in enhancing immune-mediated viral control.
authors.affiliation: Ragon Institute of Massachusetts General Hospital, Boston, USA.
authors.forename: Mathias
authors.initials: M
authors.lastname: Lichterfeld
authors.forename: Rajesh T
authors.initials: RT
authors.lastname: Gandhi
authors.forename: Rachel P
authors.initials: RP
authors.lastname: Simmons
authors.forename: Theresa
authors.initials: T
authors.lastname: Flynn
authors.forename: Amy
authors.initials: A
authors.lastname: Sbrolla
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
authors.forename: Nesli
authors.initials: N
authors.lastname: Basgoz
authors.forename: Stanley
authors.initials: S
authors.lastname: Mui
authors.forename: Katie
authors.initials: K
authors.lastname: Williams
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.forename: Nicole
authors.initials: N
authors.lastname: Burgett-Yandow
authors.forename: Gilbert
authors.initials: G
authors.lastname: Roy
authors.forename: Michel
authors.initials: M
authors.lastname: Janssens
authors.forename: Louise
authors.initials: L
authors.lastname: Pedneault
authors.forename: Pierre
authors.initials: P
authors.lastname: Vandepapelière
authors.forename: Marguerite
authors.initials: M
authors.lastname: Koutsoukos
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Demoitié
authors.forename: Patricia
authors.initials: P
authors.lastname: Bourguignon
authors.forename: Lisa
authors.initials: L
authors.lastname: McNally
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000502:physiology; D049109:Cell Proliferation; D004311:Double-Blind Method; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D022223:Vaccines, Subunit / Q000276:immunology; D055815:Young Adult; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D022223:Vaccines, Subunit; C514793:gp120 protein, Human immunodeficiency virus 1; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus