An HIVgp41 vaccine protects CD4 central memory T cells in SHIV-infected macaques

作者：Vieillard Vincent^*; Dereuddre Bosquet Nathalie; Mangeot Mederle Isabelle; Le Grand Roger; Debre Patrice

来源：Vaccine, 2012, 30(48): 6883-6891.

DOI：10.1016/j.vaccine.2012.09.004

• HIV-1
• Therapeutic vaccination
• NKp44L
• CD4(+) T cell depletion

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.
Conclusion: 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.

• 出版日期2012-11-6
• 单位中国地震局