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Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections.
- Source :
- Nature Communications; 6/22/2023, Vol. 14 Issue 1, p1-13, 13p
- Publication Year :
- 2023
-
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<superscript>+</superscript> and CD8<superscript>+</superscript> T cells. Co-culturing CD4<superscript>+</superscript> with autologous CD8<superscript>+</superscript> T cells from ART-suppressed HIV<superscript>+</superscript> donors with N6/αCD3-αCD28, results in activation of latently-infected cells and their elimination by activated CD8<superscript>+</superscript> T cells. This trispecific antibody mediates CD4<superscript>+</superscript> and CD8<superscript>+</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 14
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 164473031
- Full Text :
- https://doi.org/10.1038/s41467-023-39265-z