A Bispecific Biologic That Robustly Reverses HIV-1 and SIV Latency
- 1Columbia University Vagelos College of Physicians and Surgeons
Abstract
Antiretroviral therapy suppresses HIV-1 replication but cannot eliminate the latent viral reservoir persisting in memory CD4 T cells. Existing latency reversal candidates have yet to achieve robust viral reactivation at tolerable doses. We engineered T4IL15{triangleup}, a bispecific biologic that selectively delivers IL-15 signaling to memory CD4 T cells, with minimal off-target stimulation. T4IL15{triangleup} reactivated latent virus in 94% (48/51) of clinical samples ex vivo, 75% (15/20) of administrations in HIV-1-infected and ART-suppressed humanized mice, and 100% (6/6) of SIV-infected and ART-suppressed rhesus macaques at doses well tolerated. We also found that off-target stimulation of non-CD4 cells hindered HIV-1 reactivation ex vivo. T4IL15{triangleup} provides a robust reactivation platform that could complement other reservoir-elimination strategies toward an HIV-1 cure.
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BibTeX
@misc{huang2026bispecific,
title = {{A Bispecific Biologic That Robustly Reverses HIV-1 and SIV Latency}},
author = {Y. Huang and M. S. Nair and J. Yu and S. Chong and H. Hong and H. Mohri and H. Takata and B. D. Varco-Merth and A. Marenco and J. D. Lifson and L. Ndhlovu and A. Bowen and L. Trautmann and S. Vasan and T.-W. Chun and A. A. Okoye and D. D. Ho},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.06.757104},
url = {https://www.biorxiv.org/content/10.64898/2026.10.06.757104v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - A Bispecific Biologic That Robustly Reverses HIV-1 and SIV Latency
AU - Y. Huang
AU - M. S. Nair
AU - J. Yu
AU - S. Chong
AU - H. Hong
AU - H. Mohri
AU - H. Takata
AU - B. D. Varco-Merth
AU - A. Marenco
AU - J. D. Lifson
AU - L. Ndhlovu
AU - A. Bowen
AU - L. Trautmann
AU - S. Vasan
AU - T.-W. Chun
AU - A. A. Okoye
AU - D. D. Ho
PY - 2026
DA - 2026/10/06
PB - bioRxiv
DO - 10.64898/2026.10.06.757104
UR - https://www.biorxiv.org/content/10.64898/2026.10.06.757104v1
AB - Antiretroviral therapy suppresses HIV-1 replication but cannot eliminate the latent viral reservoir persisting in memory CD4 T cells. Existing latency reversal candidates have yet to achieve robust viral reactivation at tolerable doses. We engineered T4IL15{triangleup}, a bispecific biologic that selectively delivers IL-15 signaling to memory CD4 T cells, with minimal off-target stimulation. T4IL15{triangleup} reactivated latent virus in 94% (48/51) of clinical samples ex vivo, 75% (15/20) of administrations in HIV-1-infected and ART-suppressed humanized mice, and 100% (6/6) of SIV-infected and ART-suppressed rhesus macaques at doses well tolerated. We also found that off-target stimulation of non-CD4 cells hindered HIV-1 reactivation ex vivo. T4IL15{triangleup} provides a robust reactivation platform that could complement other reservoir-elimination strategies toward an HIV-1 cure.
ER -