Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults
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Edward Carr Hermaleigh Townsley Mary Wu Katalin Wilkinson Philip Hobson Dina Levi Sina Namjou Harriet Mears Agnieszka Hobbs Martina Ragno Lou S Herman Ruth Harvey Chris Bailey Ashley Fowler Emine Hatipoglu Yenting Ngai Bobbi Clayton Murad Miah Philip Bawumia Mauro Miranda Callie Smith Chelsea Sawyer Gavin Kelly Viyaasan Mahalingasivam Bang Zheng Stephen JW Evans Vincenzo Libri Andy Riddell Jerome Nicod Nicola O’Reilly Michael Howell Bryan Williams Robert Wilkinson George Kassiotis Charles Swanton Sonia Gandhi Rupert Beale David LV Bauer Emma Wall
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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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bioRxiv
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