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.
Competing Interest Statement
CSw reports interests unrelated to this Correspondence: grants from BMS, Ono-Pharmaceuticals, Boehringer-Ingelheim, Roche-Ventana, Pfizer and Archer Dx, unrelated to this work; personal fees from Genentech, Sarah Canon Research Institute, Medicxi, Bicycle Therapeutics, GRAIL, Amgen, AstraZeneca, BMS, Illumina, GlaxoSmithKline, MSD, and Roche-Ventana, unrelated to this work; and stock options from Apogen Biotech, Epic Biosciences, GRAIL, and Achilles Therapeutics, unrelated to this Correspondence. SGam reports funding from AstraZeneca to evaluate monoclonal antibodies subsequent to this work. DLVB reports grants from AstraZeneca unrelated to this work. The authors have no additional financial interests.