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

[tetano]

Cell Rep


. 2022 Jun 13;111013.
doi: 10.1016/j.celrep.2022.111013. Online ahead of print.
Temporal associations of B and T cell immunity with robust vaccine responsiveness in a 16-week interval BNT162b2 regimen


Manon Nayrac ¹ , Mathieu Dubé ² , Gérémy Sannier ¹ , Alexandre Nicolas ¹ , Lorie Marchitto ¹ , Olivier Tastet ² , Alexandra Tauzin ¹ , Nathalie Brassard ² , Raphaël Lima-Barbosa ³ , Guillaume Beaudoin-Bussières ¹ , Dani Vézina ² , Shang Yu Gong ⁴ , Mehdi Benlarbi ² , Romain Gasser ¹ , Annemarie Laumaea ¹ , Jérémie Prévost ¹ , Catherine Bourassa ² , Gabrielle Gendron-Lepage ² , Halima Medjahed ² , Guillaume Goyette ² , Gloria-Gabrielle Ortega-Delgado ² , Mélanie Laporte ² , Julia Niessl ¹ , Laurie Gokool ² , Chantal Morrisseau ² , Pascale Arlotto ² , Jonathan Richard ¹ , Justin Bélair ³ , Alexandre Prat ⁵ , Cécile Tremblay ¹ , Valérie Martel-Laferrière ¹ , Andrés Finzi ⁶ , Daniel E Kaufmann ⁷



Affiliations

• PMID: 35732172
• DOI: 10.1016/j.celrep.2022.111013

Abstract

Spacing of BNT162b2 mRNA doses beyond 3 weeks raises concerns about vaccine efficacy. We longitudinally analyze 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 elicits robust RBD-specific B cell responses whose kinetics differs between cohorts, the second dose leading to increased magnitude in naive participants only. While boosting does not increase magnitude of CD4⁺ T cell responses further compared with the first dose, unsupervised clustering of single-cell features reveals phenotypic and functional shifts over time and between cohorts. Integrated analysis shows longitudinal immune component-specific associations, with early T helper responses post first dose correlating with B cell responses after the second dose, and memory T helper 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.

Keywords: AIM assay; B cells; CD4 T cell; CD4 T cell help; CD8 T cell; COVID-19; CP: Immunology; SARS-CoV-2; Spike glycoproteins; coronavirus; humoral responses; immunological memory; longer interval; mRNA vaccine; vaccine regimen.