Population shift in antibody immunity following the emergence of a SARS-CoV-2 variant of concern

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) exhibit escape from pre-existing immunity and elicit variant-specific immune responses. In South Africa, the second wave of SARS-CoV-2 infections was driven by the Beta VOC, which coincided with the country-wide National COVID-19 Antibody Survey (NCAS). The NCAS was conducted between November 2020 and February 2021 to understand the burden of SARS-CoV-2 infection through seroprevalence. We evaluated 649 NCAS sera for spike binding and pseudovirus neutralizing antibodies. We classified individuals as ancestral or D614G neutralizers (114/649), Beta neutralizers (96/649), double neutralizers (375/649) or non-neutralizers (62/649). We observed a consistent decrease in preferential neutralization against the D614G variant from 68 to 18% of individuals over the four sampling months. Concurrently, samples with equivalent neutralization of both variants, or with enhanced neutralization of the Beta variant, increased from 32 to 82% of samples. Neutralization data showed that geometric mean titers (GMTs) against D614G dropped 2.4-fold, while GMTs against Beta increased 2-fold during this same period. A shift in population humoral immunity in favor of Beta-directed or cross-neutralizing antibody responses, paralleled the increase in genomic frequency of the Beta variant in South Africa. Understanding similar population immunity shifts could elucidate immunity gaps that drive SARS-CoV-2 evolution.