학술논문
Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections
Document Type
Original Paper
Author
Promsote, Wanwisa; Xu, Ling; Hataye, Jason; Fabozzi, Giulia; March, Kylie; Almasri, Cassandra G.; DeMouth, Megan E.; Lovelace, Sarah E.; Talana, Chloe Adrienna; Doria-Rose, Nicole A.; McKee, Krisha; Hait, Sabrina Helmold; Casazza, Joseph P.; Ambrozak, David; Beninga, Jochen; Rao, Ercole; Furtmann, Norbert; Birkenfeld, Joerg; McCarthy, Elizabeth; Todd, John-Paul; Petrovas, Constantinos; Connors, Mark; Hebert, Andrew T.; Beck, Jeremy; Shen, Junqing; Zhang, Bailin; Levit, Mikhail; Wei, Ronnie R.; Yang, Zhi-yong; Pegu, Amarendra; Mascola, John R.; Nabel, Gary J.; Koup, Richard A.
Source
Nature Communications. 14(1)
Subject
Language
English
ISSN
2041-1723
Abstract
Agents that can simultaneously activate latent HIV, increase immune activation and enhance the killing of latently-infected cells represent promising approaches for HIV cure. Here, we develop and evaluate a trispecific antibody (Ab), N6/αCD3-αCD28, that targets three independent proteins: (1) the HIV envelope via the broadly reactive CD4-binding site Ab, N6; (2) the T cell antigen CD3; and (3) the co-stimulatory molecule CD28. We find that the trispecific significantly increases antigen-specific T-cell activation and cytokine release in both CD4+ and CD8+ T cells. Co-culturing CD4+ with autologous CD8+ T cells from ART-suppressed HIV+ donors with N6/αCD3-αCD28, results in activation of latently-infected cells and their elimination by activated CD8+ T cells. This trispecific antibody mediates CD4+ and CD8+ T-cell activation in non-human primates and is well tolerated in vivo. This HIV-directed antibody therefore merits further development as a potential intervention for the eradication of latent HIV infection.
One of the main hurdles to curing HIV infection are viral reservoirs. Here, the authors develop a trispecific antibody and demonstrate its ability to simultaneously activate and target latently HIV−1 infected cells for elimination by T cells as an alternative strategy for HIV cure.
One of the main hurdles to curing HIV infection are viral reservoirs. Here, the authors develop a trispecific antibody and demonstrate its ability to simultaneously activate and target latently HIV−1 infected cells for elimination by T cells as an alternative strategy for HIV cure.