COVID-19 vaccines have been hugely successful in preventing severe disease. However, waning of immunity and immune evasion by viral variants mean that boosters will continue to be required. Reporting in Science, Mao et al. describe a vaccination strategy, which they call ‘prime and spike’ (P&S), where immunization with a mRNA-based vaccine is boosted through intranasal administration of unadjuvanted spike protein. In a mouse model of lethal SARS-CoV-2 infection, P&S induced robust tissue-specific immune memory and provided superior protection compared to a traditional mRNA-vaccine prime-boost regimen. Similar results were obtained in Syrian hamsters, where P&S also reduced viral transmission. Moreover, boosting with the heterologous SARS-CoV-1 spike protein resulted in robust responses against both SARS-CoV-1 and -CoV-2, indicating that it may also be suitable for the rapid adaptation to new variants.