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SARS-CoV-2 vaccines elicit differential Fc effector functions
Nelia P Manamela1,2, Boitumelo M Motsoeneng1,2, Holly Spencer1,2
1South African Medical Research Council Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
BNT162b2 vaccines show superior antibody responses, including neutralization and Fc effector functions like antibody-dependent cellular cytotoxicity (ADCC), compared to adenoviral vaccines. This highlights potential for optimizing vaccine design for enhanced protection against SARS-CoV-2.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Fc effector functions are crucial for vaccine-mediated protection against severe SARS-CoV-2 infection, complementing neutralization.
- The differential coordination and cross-reactivity of these functions across various vaccine platforms remain incompletely understood.
Purpose of the Study:
- To analyze and compare the binding, neutralization, and Fc effector functions (ADCC, ADCP, ADCD) elicited by BNT162b2, Ad26.CoV2.S, and ChAdOx1 nCoV-19 vaccines.
- To investigate the coordination and cross-reactivity of these immune responses across different vaccine modalities.
Main Methods:
- Secondary analysis of clinical trial data for three SARS-CoV-2 vaccines: BNT162b2, Ad26.CoV2.S, and ChAdOx1 nCoV-19.
- Measurement of antibody-dependent cellular cytotoxicity (ADCC), phagocytosis (ADCP), and complement deposition (ADCD) alongside binding and neutralization assays.
Main Results:
- BNT162b2 elicited the highest levels of binding, neutralization, ADCC, and ADCP. Significant differences in Fc effector functions were observed across vaccine types.
- Ad26.CoV2.S showed low ADCD activity pre-boost, which increased significantly post-boost. BNT162b2 demonstrated higher cross-reactive neutralization, ADCC, and ADCP than adenoviral vaccines.
- ChAdOx1 nCoV-19 exhibited higher cross-reactivity for ADCD. Functional coordination varied by vaccine modality, with BNT162b2 showing correlations between neutralization/binding and ADCC, while Ad26.CoV2.S correlated with ADCD.
Conclusions:
- Vaccine modality significantly influences the profile and coordination of Fc effector functions and neutralization.
- BNT162b2 demonstrates a robust polyfunctional profile, suggesting its potential for broad protection.
- Findings support the optimization of Fc effector functions in vaccine design for improved polyfunctional immune responses against SARS-CoV-2.
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