Measurement of binding antibodies to SARS-CoV-2 variants elicited by natural infection and COVID-19 vaccines in a sub-Saharan African population

Data on immune responses to COVID-19 vaccination in West and Central Africa remain limited, particularly with respect to antibody (Ab) binding across SARS-CoV-2 variants and for different types of vaccine platforms. We assessed anti-spike (anti-S) antibody binding to nine variants using the Meso Scale Discovery 10 plex assay (MSD) in 96 participants from the InVITE cohort, residing in the Democratic Republic of Congo, Guinea, Liberia, and Mali. Pre-vaccination anti-S seropositivity was determined with the Quanterix assay, and 48 participants each were selected from seronegative (no prior infection) and seropositive (prior infection) groups. Participants received either an mRNA, adenovirus-vectored, or inactivated virus vaccine. Anti-S binding levels were measured at baseline visit(V1) and the visit two months following completion of the primary vaccination series (V2). Regression models were applied to examine the effects of variant group, prior infection status, and vaccine platform on antibody binding responses. At V1, seropositive participants had significantly higher antibody binding than seronegative individuals (fold change 15.65, 95% CI: 10.13–24.18). Binding to ancestral variants (Wuhan, Alpha, Beta, Delta) exceeded that to Omicron (BA.1, BA.2, BA.2.12.1, BA.2.75, BA.5) variants (fold change 3.7, 95% CI: 3.53–3.86). At V2, antibody levels rose substantially across both groups, with the greatest fold increases in seronegative individuals. mRNA vaccines elicited the strongest responses, particularly in the seronegative group (fold change vs. adenovirus vaccines 6.93 for ancestral and 7.57 for Omicron). Post-vaccination, differences between seronegative and seropositive groups were no longer significant. Vaccination markedly enhanced antibody binding across variants, with mRNA vaccines generating the highest responses. Prior infection conferred an advantage at baseline, but vaccination equalized responses across serostatus groups. These findings highlight the strong immunogenicity of mRNA vaccines and underscore the value of completing the full vaccination series in previously uninfected individuals in West and Central Africa. ClinicalTrials.gov, NCT05096091, date of registration: October 26, 2021, Clinical trial registry: https://clinicaltrials.gov/study/NCT05096091?term=NCT05096091&rank=1#study-overview