Transient regulatory T cell manipulation is limited by anti-antibody responses in HIV-1 envelope immunized rhesus...

CD25⁺ FoxP3⁺ CD4⁺ regulatory T (Treg) cells promote immune tolerance. We studied germinal center responses and HIV-1 antibody development in rhesus macaques (RMs) immunized with sequential CH505 gp120 envelopes (Envs), with or without anti-CD25 monoclonal antibody (mAb). Plasma Env antibody levels and CD4 binding sited-directed responses were similar across groups. Treg and CXCR5-expressing follicular Treg cell frequency dropped more than two times after the first anti-CD25 infusion but not later ones. Transient Treg disruption was associated with a reduced proportion of vaccine-elicited B cell clonal lineages in lymphoid tissue, but did not result in neutralization breadth. Anti-CD25-treated RMs developed anti-drug antibodies, correlating with reduced plasma mAb levels after subsequent infusions. Germinal center responses were modified by Treg perturbation intended to induce HIV-1 bnAbs, but this effect was curtailed by anti-antibody responses. This may have implications for vaccination in persons receiving immune modulating drugs for transplants or other medical conditions.