SARS-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 neutralization, ADCC and ADCP than the adenoviral vaccines, while ChAdOx1 nCoV-19 exhibited higher ADCD cross-reactivity. Coordination between functions all varied by modality, with vaccination eliciting neutralization and binding correlations with ADCC for BNT162b2, but with ADCD following Ad26.CoV2.S vaccination. This supports the optimization of Fc effector functions for improved polyfunctional vaccine design.