Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections
oleh: Wanwisa Promsote, Ling Xu, Jason Hataye, Giulia Fabozzi, Kylie March, Cassandra G. Almasri, Megan E. DeMouth, Sarah E. Lovelace, Chloe Adrienna Talana, Nicole A. Doria-Rose, Krisha McKee, Sabrina Helmold Hait, Joseph P. Casazza, David Ambrozak, Jochen Beninga, Ercole Rao, Norbert Furtmann, Joerg Birkenfeld, Elizabeth McCarthy, John-Paul Todd, Constantinos Petrovas, Mark Connors, Andrew T. Hebert, Jeremy Beck, Junqing Shen, Bailin Zhang, Mikhail Levit, Ronnie R. Wei, Zhi-yong Yang, Amarendra Pegu, John R. Mascola, Gary J. Nabel, Richard A. Koup
| Format: | Article |
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| Diterbitkan: | Nature Portfolio 2023-06-01 |
Deskripsi
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.