vaccine strategy against AIDS: An HIV gp41 peptide immunization prevents NKp44L expression and CD4⁺ T cell depletion in SHIV-infected macaques

We previously showed that a gp41 peptide (3S) induces expression of a natural killer (NK) ligand (NKp44L) on CD4⁺ T cells during HIV-1 infection and that those cells are highly sensitive to NK lysis. In HIV-infected patients, anti-3S antibodies are associated with the maintenance of CD4⁺ T cell counts close to their baseline values, and CD4⁺ T cells decrease with the antibody titer. This study sought to determine whether anti-3S immunization could prevent NKp44L expression on these CD4⁺ T cells in vivo and inhibits the subsequent decline in CD4⁺ T cell counts by immunizing macaques with 3S and then infecting them with simian HIV₁₆₂P₃. The results show that anti-3S antibodies inhibited NKp44L expression and NK activity and cytotoxicity. They also decreased the apoptosis rate of CD4⁺ T cells in peripheral blood and lymph nodes. These data raise questions about the pathogenesis of HIV and present opportunities for both preventive and therapeutic HIV vaccine strategies.