title: Comprehensive analysis of virus-specific T-cells provides clues for the failure of therapeutic immunization with ALVAC-HIV vaccine.
abstract: BACKGROUND
  HIV-specific T-cell-based vaccines have been extensively studied in both prevention and therapeutic settings, with most studies failing to show benefit, and some suggesting harm. We previously performed a multicenter, double-blind, placebo-controlled phase II clinical trial in which 65 antiretroviral-treated patients were randomized to receive an HIV-1 recombinant canarypox vaccine (vCP1452) or placebo, followed by analytical treatment interruption. Patients exposed to vaccine had higher levels of viral replication and more rapid time to treatment resumption.
  
  
  OBJECTIVE
  In the present study we report the results from extensive immunological investigations to test whether the preferential expansion of HIV-specific CD4(+), rather than CD8(+) T cells, could account for these unexpected results.
  
  
  METHODS
  Polychromatic flow cytometry was used to characterize the functional and phenotypic profile of antigen-specific CD8(+) and CD4(+) T cells induced by the immunization.
  
  
  RESULTS
  We found a significant increase in HIV-specific CD4(+) T cells producing IFN-γ and IL-2 in the 4 injections arm compared to the placebo arm following vaccination. In contrast, no difference was observed following vaccination in the phenotype and functional capacity within the CD8(+) T-cell compartment. Neither HLA biases, nor immune hyper-activation, or Env-specific facilitating antibodies were associated with the enhanced virus rebound observed in vaccinees.
  
  
  CONCLUSIONS
  Our data suggest that a vaccine-induced transient activation of HIV-specific CD4(+) but not CD8(+) T cells may have a detrimental effect on HIV outcomes. These findings may provide a mechanistic basis for higher rates of HIV acquisition or replication that have been associated with some T-cell vaccines.
authors.affiliation: UPMC Univ Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Papagno
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.forename: Lambert
authors.initials: L
authors.lastname: Assoumou
authors.forename: Robert L
authors.initials: RL
authors.lastname: Murphy
authors.forename: Felipe
authors.initials: F
authors.lastname: Garcia
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Martin
authors.initials: M
authors.lastname: Larsen
authors.forename: Martine
authors.initials: M
authors.lastname: Braibant
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D028121:Canarypox virus / Q000276:immunology; D004311:Double-Blind Method; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology; D015497:HIV-1; D006801:Humans; D012367:RNA, Viral / Q000187:drug effects / Q000276:immunology*; D019562:Viral Load; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use*
chemical_list: C078788:ALVAC vaccine; D057134:Antibodies, Neutralizing; D012367:RNA, Viral; D014765:Viral Vaccines