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

Nayrac, M.; Dube, M.; Sannier, G.; Nicolas, A.; Marchitto, L.; Tastet, O.; Tauzin, A.; Brassard, N.; Beaudoin-Bussieres, G.; Vezina, D.; Gong, S. Y.; Benlarbi, M.; Gasser, R.; Laumaea, A.; Bourassa, C.; Gendron-Lepage, G.; Medjahed, H.; Goyette, G.; Ortega-Delgado, G.-G.; Laporte, M.; Niessl, J.; Gokool, L.; Morrisseau, C.; Arlotto, P.; Richard, J.; Tremblay, C.; Martel-Laferriere, V.; Finzi, A.; Kaufmann, D. E.

doi:10.1101/2021.12.18.473317

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bioRxiv · 10.1101/2021.12.18.473317

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

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Abstract

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.

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Nayrac, M., Dube, M., Sannier, G., Nicolas, A., Marchitto, L., Tastet, O., Tauzin, A., Brassard, N., Beaudoin-Bussieres, G., Vezina, D., Gong, S. Y., Benlarbi, M., Gasser, R., Laumaea, A., Bourassa, C., Gendron-Lepage, G., Medjahed, H., Goyette, G., Ortega-Delgado, G.-G., Laporte, M., Niessl, J., Gokool, L., Morrisseau, C., Arlotto, P., Richard, J., Tremblay, C., Martel-Laferriere, V., Finzi, A., Kaufmann, D. E.. 2021-12-21. Temporal associations of B and T cell immunity with robust vaccine responsiveness in a 16-week interval BNT162b2 regimen. https://doi.org/10.1101/2021.12.18.473317

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