Immune imprinting and next-generation coronavirus vaccines

Vaccines based on historical virus isolates provide limited protection from continuously evolving RNA viruses, such as influenza viruses or coronaviruses, which occasionally spill over between animals and humans. Despite repeated booster immunizations, population-wide declines in the neutralization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have occurred. This has been compared to seasonal influenza vaccinations in humans, where the breadth of immune responses induced by repeat exposures to antigenically distinct influenza viruses is confounded by pre-existing immunity—a mechanism known as imprinting. Since its emergence, SARS-CoV-2 has evolved in a population with partial immunity, acquired by infection, vaccination or both. Here we critically examine the evidence for and against immune imprinting in host humoral responses to SARS-CoV-2 and its implications for coronavirus disease 2019 (COVID-19) booster vaccine programmes.C.Q.H. received funding from the Cambridge Commonwealth, European & International Trust, Croucher Foundation and St John’s College, Cambridge. J.L.H., S.V. and G.W.C. received funding from the Bill & Melinda Gates Foundation and InnovateUK to develop a universal flu vaccine and from CEPI to develop a broadly protective betacoronavirus vaccine. J.L.H., S.V. and DIOSynVax Ltd. received funding from InnovateUK to perform a Phase 1 clinical trial of a needle-free pan-sarbecovirus vaccine