journals.asm.org
Fc-engineered broadly neutralizing antibodies overcome cytokine-induced CD16 cleavage to drive potent ADCC against diverse HIV-1 strains | mBio
Eradicating latent HIV reservoirs remains a global health priority as it would liberate millions of people living with HIV (PLWH) from the economic and physiological burdens of lifelong antiretroviral therapy (ART). By utilizing a primary human cell model that resembles in vivo conditions across diverse viral strains, we identified that simply preventing CD16 receptor shedding from natural killer (NK) cells is insufficient to improve HIV-1 clearance. Instead, we demonstrated that enhancing the binding of antibodies to the CD16 receptor enables NK cells to overcome viral immune evasion and the loss of CD16 expression. This allows for potent elimination of infected cells through antibody-dependent cellular cytotoxicity (ADCC). These findings provide a clear strategy for designing more effective “kill” components in future therapeutic strategies.
