title: An HIVgp41 vaccine protects CD4 central memory T cells in SHIV-infected macaques.
abstract: BACKGROUND
  The immunodeficiency defining AIDS results from a progressive decline in the number of CD4(+) T cells. Although no single viral protein is likely to be the sole effector of immune impairment, the gp41 envelope protein is believed to contribute significantly to AIDS pathogenesis. We have shown that 3S, a unique motif of gp41, is highly conserved in HIV-1 strains and specifically induces NKp44L, a ligand of the natural cytotoxicity receptor NKp44, on CD4(+) T cells, rendering them sensitive to NK lysis. We therefore hypothesized that a 3S/gp41 vaccine strategy designed to modulate the NK cell compartment might improve CD4(+) T cell resistance, independently of any effect on viral load.
  
  
  METHODS
  Nine macaques were chronically infected with the SHIV163P3; four were then immunized with the 3S/gp41 peptide and five with the carrier alone. Frequency of CD4(+) T cell subsets, proliferation, cell activation and apoptosis were analyzed in the periphery and the lymph nodes, spleen and rectum by flow cytometry.
  
  
  RESULTS
  The anti-3S antibodies prevented NKp44L expression on CD4(+) T cells in vivo and subsequently preserved the CD4(+) central memory T cells in 3S/gp41-vaccinated animals. They also limited the NK cytotoxic activity against autologous CD4(+) T cells, the cell activation, the proliferation, and the apoptosis in peripheral blood and secondary lymphoid tissues remained intact.
  
  
  CONCLUSIONS
  These data suggest a new paradigm for AIDS vaccine development, aimed at generating specific responses to protect a specific subset of CD4(+) T cells from attack by activated NK cells.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR-S 945, Laboratoire Immunité et Infection, Paris 75651, France. vincent.vieillard@upmc.fr
authors.forename: Vincent
authors.initials: V
authors.lastname: Vieillard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mangeot-Méderlé
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D017209:Apoptosis; D001769:Blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D005434:Flow Cytometry; D015483:HIV Antibodies / Q000097:blood; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007156:Immunologic Memory; D008198:Lymph Nodes / Q000276:immunology; D008251:Macaca; D012007:Rectum / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D013154:Spleen / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41