biostudies-literatureUnknown28(8)Manamela NPIn addition to neutralization, Fc effector function contributes to vaccine-mediated protection against severe SARS-CoV-2 infection. However, differential coordination and cross-reactivity of Fc effector functions across vaccines is not clearly defined. A secondary analysis of three vaccines with BNT162b2, Ad26.CoV2.S (NCT04838795), and ChAdOx1 nCoV-19 (NCT04444674) reveals that BNT162b2 elicits the highest levels of binding, neutralization, and Fc effector function with antibody-dependent cellular cytotoxicity (ADCC), phagocytosis (ADCP), and complement deposition (ADCD) significantly differing by vaccine modality. Ad26.CoV2.S showed low ADCD activity before a homologous boost, which significantly increased this function. BNT162b2 vaccination triggered higher levels of cross-reactive neutriScience113084https://www.ebi.ac.uk/biostudies/studies/S-EPMC12309960biostudies-literatureSARS-CoV-2 vaccines elicit differential Fc effector functions.PMC12309960Mzindle NHermanus TAyres FGray GGRichardson SIMotsoeneng BMMoore PLSpencer HMakhado ZSerage RManamela NPMadhi SABekker LGfalseSARS-CoV-2 vaccines elicit differential Fc effector functions.In addition to neutralization, Fc effector function contributes to vaccine-mediated protection against severe SARS-CoV-2 infection. However, differential coordination and cross-reactivity of Fc effector functions across vaccines is not clearly defined. A secondary analysis of three vaccines with BNT162b2, Ad26.CoV2.S (NCT04838795), and ChAdOx1 nCoV-19 (NCT04444674) reveals that BNT162b2 elicits the highest levels of binding, neutralization, and Fc effector function with antibody-dependent cellular cytotoxicity (ADCC), phagocytosis (ADCP), and complement deposition (ADCD) significantly differing by vaccine modality. Ad26.CoV2.S showed low ADCD activity before a homologous boost, which significantly increased this function. BNT162b2 vaccination triggered higher levels of cross-reactive neutr2025-01-01T00:00:00Z2025 Aug2026-03-16T05:52:20.535Z2025-08-14T03:06:18.836ZS-EPMC123099604074048510.1016/j.isci.2025.113084