title: Targeting concatenated HIV antigens to human CD40 expands a broad repertoire of multifunctional CD4+ and CD8+ T cells.
abstract: OBJECTIVE
  Targeting HIV antigens directly to dendritic cells using monoclonal antibodies against cell-surface receptors has been shown to evoke potent cellular immunity in animal models. The objective of this study was to configure an anti-human CD40 antibody fused to a string of five highly conserved CD4 and CD8 T-cell epitope-rich regions of HIV-1 Gag, Nef and Pol (αCD40.HIV5pep), and then to demonstrate the capacity of this candidate therapeutic vaccine to target these HIV peptide antigens to human dendritic cells to expand functional HIV-specific T cells.
  
  
  METHODS
  Antigen-specific cytokine production using intracellular flow cytometry and multiplex bead-based assay, and suppression of viral inhibition, were used to characterize the T cells expanded by αCD40.HIV5pep from HIV-infected patient peripheral blood mononuclear cell (PBMC) and dendritic cell/T-cell co-cultures.
  
  
  RESULTS
  This candidate vaccine expands memory CD4 and CD8 T cells specific to multiple epitopes within all five peptide regions across a wide range of major histocompatibility complex (MHC) haplotypes from HIV-infected patient PBMC and dendritic cell/T-cell co-cultures. These in vitro expanded HIV antigen-specific CD4 and CD8 T cells produce multiple cytokines and chemokines. αCD40.HIV5pep-expanded CD8 T cells have characteristics of cytotoxic effector cells and are able to kill autologous target cells and suppress HIV-1 replication in vitro.
  
  
  CONCLUSIONS
  Our data demonstrate the therapeutic potential of this CD40-targeting HIV candidate vaccine in inducing a broad repertoire of multifunctional T cells in patients.
authors.affiliation: aBaylor Institute for Immunology Research, Dallas, Texas, USA bANRS HIV Vaccine Network/Vaccine Research Institute, Paris cEcole doctorale Sciences de la Vie et de la Santé, Université Paris-Est, Créteil, France dINSERM U899 eNorth Texas Infectious Diseases, Dallas, Texas, USA fUniversité Paris-Est, Faculté de Médecine, INSERM U955 gAssistance Publique-Hôpitaux de Paris, Groupe Henri-Mondor Albert-Chenevier, service d'immunologie clinique, Créteil, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Flamar
authors.forename: Yaming
authors.initials: Y
authors.lastname: Xue
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Zurawski
authors.forename: Monica
authors.initials: M
authors.lastname: Montes
authors.forename: Bryan
authors.initials: B
authors.lastname: King
authors.forename: Louis
authors.initials: L
authors.lastname: Sloan
authors.forename: SangKon
authors.initials: S
authors.lastname: Oh
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D015488:HIV Antigens; D011993:Recombinant Fusion Proteins