Env-specific antibodies promote post-treatment control in SIV-infected macaques
Year: 2026
Type: article
Abstract: Viral latency reversal was observed in simian immunodeficiency virus (SIV)-infected rhesus macaques receiving antiretroviral therapy (ART), CD8α lymphocyte depletion and N-803 immunotherapy. However, this therapeutic approach did not reduce the viral reservoir size and treatment interruption resulted in rapid virus rebound. Here, to address this shortfall, we used four anti-SIV Env-specific rhesus IgG1 monoclonal antibodies (RhmAbs) that recognize unique targets on the SIV envelope. SIV mac239 -infected macaques were treated with ART only (group 1); ART + RhmAbs (group 2); or ART + RhmAbs + CD8α-depletion + N-803 (group 3). Robust latency reversal was only achieved in group 3. Viraemia rebounded in all macaques with similar kinetics after treatment interruption. However, compared with pre-ART viral loads, a greater fold reduction in rebound viraemia was seen in groups 2 and 3 and post-treatment control (PTC) required SIV RhmAbs. CD4 + T cells from macaques with PTC maintained low levels of intact SIV proviruses off ART and expressed increased interferon and decreased TGF-β signalling genes. This antiviral gene expression profile was also observed in CD4 + T cells with lower human immunodeficiency virus (HIV)-DNA content from ART-treated people with HIV. These results suggest that reduced virus production may contribute to PTC following ART interruption and provide a target for immune-based strategies to achieve durable viral control.
Source: Nature Microbiology
Authors: Vidisha Singh, Divine Burgess, Jordan Goldy, Amir Dashti, Hannah King, Emily Fray, Anushka Singhal, Maud Mavigner, Nils Schoof, Zain Siddiqi, Rosemarie D. Mason, Jeffrey T. Safrit, Vinh Dinh, Deanna Kulpa, Rafick-Pierre Sékaly, Mirko Paiardini, Jeffrey D. Lifson, Robert F. Siliciano, Janet D. Siliciano, Mario Roederer, Ashish Sharma, Guido Silvestri, Ann Chahroudi
Institutions: Emory University, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center, Johns Hopkins University, Johns Hopkins Medicine, Children's Healthcare of Atlanta, Emory National Primate Research Center, ImmunityBio (United States), Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. (United States)
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W7225748145