Are variant-specific vaccines warranted?

The efficacy of current COVID-19 vaccines wanes over time, and viral variants, particularly Omicron, have lost many of the binding sites for neutralizing antibodies — leading to large numbers of breakthrough infections in vaccinated individuals. Vaccine boosters can restore protection (at least for a few months), and variant-specific boosters are currently being trialled. In a mouse model of COVID-19, Ying et al. demonstrate that boosting with an Omicron-specific version of mRNA-1273, as compared to the ‘original’ mRNA-1273, leads to enhanced protection against Omicron. However, full vaccination with the Omicron-adapted vaccine provided poor cross-protection against the ancestral virus. Meanwhile, Gagne et al. compared mRNA-1273 and Omicron-matched booster shots in macaques that had been vaccinated with mRNA-1273 months earlier. Following challenge with Omicron, both boosters induced 70–80% cross-protective B cells and provided complete protection in the lungs as well as comparable, limited protection in the upper airways. Given the uncertainty around potential new variants, broad protection may be preferable to variant-specific protection.