Evaluating Fc-mediated antibody functions against SARS-CoV-2 in PLHIV: reduced FcγRIIIa-dependent activity and ADCC despite preserved neutralising antibodies

Background Antibody-dependent cellular cytotoxicity (ADCC) is a critical Fc-mediated immune mechanism contributing to antiviral defence. However, its functionality in people living with HIV (PLHIV) following SARS-CoV-2 exposure remains poorly understood. Objective This study evaluates the anti-Spike ADCC antibody levels, functional ADCC activity, and neutralising antibody responses in HIV-negative and HIV-positive individuals. Methodology The study included 30 samples per group. Anti-Spike ADCC-binding antibodies were measured using FcγRIIIa-binding assays, while functional ADCC activity was evaluated by rapid fluorometric antibody-dependent cellular cytotoxicity (RFADCC) assays. Neutralising antibody responses were assessed using surrogate virus neutralization assays. Results HIV-negative Spike-positive individuals exhibited significantly higher levels of ADCC antibodies compared to HIV-positive counterparts (fold response: 8.74 vs 6.23; p=0.0056). Consistently, functional ADCC activity was reduced in HIV-positive individuals (mean: 43.87%) compared to HIV-negative individuals (mean: 52.16%; p=0.03), indicating impaired Fc-mediated effector function. In contrast, neutralising antibody responses were largely preserved, with no significant difference observed between HIV-positive and HIV-negative Spike-positive groups, despite increased variability in the HIV-positive cohort. Conclusion These findings demonstrate reduced FcγRIIIa-dependent antibody activity and functional ADCC responses in PLHIV despite relatively preserved neutralising antibody responses, highlighting differences between Fc-mediated and neutralising antibody functions.