ArticleFrontiers in immunology2026
Evaluating Fc-mediated antibody functions against SARS-CoV-2 in PLHIV: reduced FcγRIIIa-dependent activity and ADCC despite preserved neutralising antibodies.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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.
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