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

## TL;DR

Disrupting regulatory T cells in monkeys with HIV vaccines briefly changes immune responses but is limited by immune reactions to the treatment itself.

## Contribution

Demonstrates that anti-CD25 treatment transiently affects Treg cells but is limited by anti-drug antibodies in HIV-vaccinated monkeys.

## Key findings

- Anti-CD25 treatment reduces Treg and follicular Treg cell frequency after the first infusion.
- Treg disruption modifies germinal center responses but does not improve antibody breadth.
- Anti-drug antibodies develop in treated monkeys, limiting the effectiveness of subsequent infusions.

## Abstract

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.

•Anti-CD25 treatment briefly perturbs Treg cell frequency in HIV Env-immunized rhesus macaques•Treg disruption alters germinal center responses but does not enhance antibody breadth•Anti-CD25-induced Treg perturbation is constrained by anti-drug immune responses

Anti-CD25 treatment briefly perturbs Treg cell frequency in HIV Env-immunized rhesus macaques

Treg disruption alters germinal center responses but does not enhance antibody breadth

Anti-CD25-induced Treg perturbation is constrained by anti-drug immune responses

Biological sciences; Immunology; Virology