Predicting the efficacy of variant-modified COVID-19 vaccine boosters

Booster vaccination for the prevention of Coronavirus Disease 2019 (COVID-19) is required to overcome loss of protection due to waning immunity and the spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Studies have assessed the ability of existing ancestral-based vaccines as well as novel variant-modified vaccine regimens to boost immunity to different variants, and a crucial question is to assess the relative benefits of these different approaches. Here we aggregate data on neutralization titers from 14 reports (three published papers, eight preprints, two press releases and notes of one advisory committee meeting) comparing booster vaccination with the current ancestral-based vaccines or variant-modified vaccines. Using these data, we compare the immunogenicity of different vaccination regimens and predict the relative protection of booster vaccines under different scenarios. We predict that boosting with ancestral vaccines can markedly enhance protection against both symptomatic and severe disease from SARS-CoV-2 variant viruses, although variant-modified vaccines may provide additional protection, even if not matched to the circulating variants. This work provides an evidence-based framework to inform choices on future SARS-CoV-2 vaccine regimens.