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Immune imprinting and next-generation coronavirus vaccines

Nature Microbiology volume 8, pages 1971–1985 (2023)Cite this article

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Abstract

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.

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Fig. 1: Immune responses to influenza virus and SARS-CoV-2 in the context of infection and vaccination.
Fig. 2: Primary exposure to a virus generates a pool of antibodies with both neutralizing and non-neutralizing paratopes.
Fig. 3: The antigenic seniority model, showing the hierarchical nature of imprinting on the antibody responses to SARS-CoV-2 and its variants.
Fig. 4: Germinal centre dynamics of imprinting—distraction, exhaustion and competitive inhibition.

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Acknowledgements

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.

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  1. Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK

    Chloe Qingzhou Huang, Sneha Vishwanath, George William Carnell, Andrew Chun Yue Chan & Jonathan Luke Heeney

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Contributions

C.Q.H. and J.L.H. conceived the main ideas for this Review. C.Q.H. researched data and wrote the Review. C.Q.H., S.V., G.W.C. and A.C.Y.C developed the figures with input from J.L.H. All authors contributed substantially to discussion of the content, and reviewed and/or edited the manuscript before submission.

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Correspondence to Jonathan Luke Heeney.

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Competing interests

J.L.H. is an employee of the University of Cambridge and the founder and CEO of DIOSynVax Ltd. J.L.H., S.V. and G.W.C. are inventors of patents on influenza and coronavirus vaccines.

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Huang, C.Q., Vishwanath, S., Carnell, G.W. et al. Immune imprinting and next-generation coronavirus vaccines. Nat Microbiol 8, 1971–1985 (2023). https://doi.org/10.1038/s41564-023-01505-9

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