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Temporal associations of B and T cell immunity with robust vaccine responsiveness in a 16-week interval BNT162b2 regimen

Manon Nayrac; Mathieu Dube; Geremy Sannier; Alexandre Nicolas; Lorie Marchitto; Olivier Tastet; Alexandra Tauzin; Nathalie Brassard; Guillaume Beaudoin-Bussieres; Dani Vezina; Shang Yu Gong; Mehdi Benlarbi; Romain Gasser; Annemarie Laumaea; Catherine Bourassa; Gabrielle Gendron-Lepage; Halima Medjahed; Guillaume Goyette; Gloria-Gabrielle Ortega-Delgado; Melanie Laporte; Julia Niessl; Laurie Gokool; Chantal Morrisseau; Pascale Arlotto; Jonathan Richard; Cecile Tremblay; Valerie Martel-Laferriere; Andres Finzi; Daniel E Kaufmann.
Preprint en Inglés | PREPRINT-BIORXIV | ID: ppbiorxiv-473317
Spacing of the BNT162b2 mRNA doses beyond 3 weeks raised concerns about vaccine efficacy. We longitudinally analyzed B cell, T cell and humoral responses to two BNT162b2 mRNA doses administered 16 weeks apart in 53 SARS-CoV-2 naive and previously-infected donors. This regimen elicited robust RBD-specific B cell responses whose kinetics differed between cohorts, the second dose leading to increased magnitude in naive participants only. While boosting did not increase magnitude of CD4+ T cell responses further compared to the first dose, unsupervised clustering analyses of single-cell features revealed phenotypic and functional shifts over time and between cohorts. Integrated analysis showed longitudinal immune component-specific associations, with early Thelper responses post-first dose correlating with B cell responses after the second dose, and memory Thelper generated between doses correlating with CD8 T cell responses after boosting. Therefore, boosting elicits a robust cellular recall response after the 16-week interval, indicating functional immune memory.