Variant-adapted COVID-19 booster vaccines

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines greatly reduced the burden of the COVID-19 pandemic and saved millions of lives (1). However, waning levels of circulating neutralizing antibodies and the continuous emergence of SARS-CoV-2 variants of concern decreased vaccine effectiveness and prompted the need for booster immunizations. Some variants are substantially antigenically distant from the ancestral strain, propelling the development of variant-adapted vaccines. The entanglement of waning immunity and viral variants in terms of immune protection, variant selection in updated vaccines, effectiveness of these vaccines in inducing de novo responses to new variants, and when to change them in the future remain outstanding knowledge gaps.