# Neutralization and ADCC reveal divergent spike-subdomain targeting across SARS-CoV-2 vaccine platforms in an African cohort

## TL;DR

This study compares how different SARS-CoV-2 vaccines affect antibody responses in Ugandan participants, showing varied immune reactions based on vaccine type.

## Contribution

The study reveals distinct immunogenetic patterns in an African cohort, highlighting vaccine-specific differences in neutralization and ADCC.

## Key findings

- BNT162b2 induced the strongest neutralizing antibody responses.
- CoronaVac led to S2-biased IgG and strong ADCC despite weaker neutralization.
- Many participants had elevated pre-vaccination S2-IgG, suggesting prior cross-reactivity.

## Abstract

Evaluating demographically diverse antibody response dynamics remains relevant to developing better vaccines against SARS-CoV-2 and related coronaviruses. Here, in 80 Ugandan study participants vaccinated with BNT162b2, CoronaVac or ChAdOx1-S, we investigated longitudinal neutralization and antibody-dependent cellular cytotoxicity (ADCC) functions, correlating these with immunoglobulin G (IgG) binding dynamics to spike subdomains, receptor-binding domain, N-terminal domain, and S2, across variants. Neutralizing and ADCC responses differed by vaccine type and IgG subdomain binding profiles. S2-IgG binding and ADCC effector function dominated the immune response to CoronaVac vaccination, while BNT162b2 induced the most potent neutralizing antibodies. Overall, we reveal intra-population diversity in antibody binding, neutralization and ADCC among vaccinated individuals, many of whom exhibited elevated pre-vaccination S2-IgG, despite presumed absence of prior infection. There was confounding by vaccination scheduling amidst ongoing waves of infection. These data reveal distinct immunogenetic patterns in a sub-Saharan African population that could inform regionally tailored vaccine strategies and global pan-coronavirus vaccine development.

•BNT162b2 elicited the broadest and strongest neutralizing antibody responses•CoronaVac induced S2-biased IgG and robust ADCC despite modest neutralization•High baseline S2-IgG revealed cross-reactivity in presumed infection-naive adults•Neutralization and ADCC mapped to distinct spike subdomains across vaccines

BNT162b2 elicited the broadest and strongest neutralizing antibody responses

CoronaVac induced S2-biased IgG and robust ADCC despite modest neutralization

High baseline S2-IgG revealed cross-reactivity in presumed infection-naive adults

Neutralization and ADCC mapped to distinct spike subdomains across vaccines

Immunology; public health