HIV-1 CD4-induced (CD4i) gp120 epitope vaccines promote B and T-cell responses that contribute to reduced viral loads in rhesus macaques.

To target the HIV CD4i envelope epitope, we primed rhesus macaques with replicating Ad-rhFLSC (HIV-1 BaL gp120 linked to macaque CD4 D1 and D2), with or without Ad-SIV gag and Ad-SIV nef . Macaques were boosted with rhFLSC protein. Memory T-cells in PBMC, bronchoalveolar lavage and rectal tissue, antibodies with neutralizing and ADCC activity, and Env-specific secretory IgA in rectal secretions were elicited. Although protective neutralizing antibody levels were induced, SHIV SF162P4 acquisition following rectal challenge was not prevented. Rapid declines in serum ADCC activity, Env-specific memory B cells in PBMC and bone marrow, and systemic and mucosal memory T cells were observed immediately post-challenge together with delayed anamnestic responses. Innate immune signaling resulting from persisting Ad replication and the TLR-4 booster adjuvant may have been in conflict and reoriented adaptive immunity. A different adjuvant paired with replicating Ad, or a longer post-prime interval allowing vector clearance before boosting might foster persistent T- and B-cell memory. [ABSTRACT FROM AUTHOR]