Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults
Author:
Carr Edward JORCID, Townsley Hermaleigh, Wu Mary YORCID, Wilkinson Katalin AORCID, Hobson Philip SORCID, Levi Dina, Namjou Sina, Mears Harriet VORCID, Hobbs Agnieszka, Ragno Martina, Herman Lou S, Harvey Ruth, Bailey Chris, Fowler Ashley SORCID, Hatipoglu Emine, Ngai Yenting, Clayton Bobbi, Miah Murad, Bawumia Philip, Miranda Mauro, Smith Callie, Sawyer Chelsea, Kelly Gavin, Mahalingasivam ViyaasanORCID, Zheng Bang, Evans Stephen JWORCID, Libri Vincenzo, Riddell Andrew, Nicod JeromeORCID, O’Reilly Nicola, Howell Michael, Williams Bryan, Wilkinson Robert JORCID, Kassiotis GeorgeORCID, Swanton Charles, Gandhi Sonia, Beale Rupert CL, Bauer David LVORCID, Wall Emma CORCID
Abstract
ABSTRACTHeterogeneity 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.
Publisher
Cold Spring Harbor Laboratory
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