Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults

Carr, E. J.; Townsley, H.; Wu, M. Y.; Wilkinson, K. A.; Hobson, P. S.; Levi, D.; Namjou, S.; Mears, H. V.; Hobbs, A.; Ragno, M.; Herman, L. S.; Harvey, R.; Bailey, C.; Fowler, A. S.; Hatipoglu, E.; Ngai, Y.; Clayton, B.; Miah, M.; Bawumia, P.; Miranda, M.; Smith, C.; Sawyer, C.; Kelly, G.; Mahalingasivam, V.; Zheng, B.; Evans, S. J.; Libri, V.; Riddell, A.; Nicod, J.; O'Reilly, N.; Howell, M.; Williams, B.; Wilkinson, R. J.; Kassiotis, G.; Swanton, C.; Gandhi, S.; Beale, R. C.; Bauer, D. L.; Wall, E. C.

doi:10.1101/2023.05.24.541920

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bioRxiv · 10.1101/2023.05.24.541920

Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults

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Abstract

Heterogeneity in SARS-CoV-2 vaccine responses is not understood. Here, we identify four patterns of live-virus neutralizing antibody responses: individuals with hybrid immunity (with confirmed prior infection); rare individuals with low responses (paucity of S1-binding antibodies); and surprisingly, two further groups with distinct serological repertoires. One group - broad responders - neutralize a range of SARS-CoV-2 variants, whereas the other - narrow responders - neutralize fewer, less divergent variants. This heterogeneity does not correlate with Ancestral S1-binding antibody, rather the quality of the serological response. Furthermore, IgDlowCD27-CD137+ B cells and CCR6+ CD4+ T cells are enriched in broad responders before dose 3. Notably, broad responders have significantly longer infection-free time after their third dose. Understanding the control and persistence of these serological profiles could allow personalized approaches to enhance serological breadth after vaccination.

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Carr, E. J., Townsley, H., Wu, M. Y., Wilkinson, K. A., Hobson, P. S., Levi, D., Namjou, S., Mears, H. V., Hobbs, A., Ragno, M., Herman, L. S., Harvey, R., Bailey, C., Fowler, A. S., Hatipoglu, E., Ngai, Y., Clayton, B., Miah, M., Bawumia, P., Miranda, M., Smith, C., Sawyer, C., Kelly, G., Mahalingasivam, V., Zheng, B., Evans, S. J., Libri, V., Riddell, A., Nicod, J., O'Reilly, N., Howell, M., Williams, B., Wilkinson, R. J., Kassiotis, G., Swanton, C., Gandhi, S., Beale, R. C., Bauer, D. L., Wall, E. C.. 2023-05-25. Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults. https://doi.org/10.1101/2023.05.24.541920

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