An extended SARS-CoV-2 mRNA vaccine prime-boost interval enhances B cell immunity with limited impact on T cells

Alexandre Nicolas; Gérémy Sannier; Mathieu Dubé; Manon Nayrac; Alexandra Tauzin; Mark M Painter; Rishi R Goel; Mélanie Laporte; Gabrielle Gendron-Lepage; Halima Medjahed; Justine C Williams; Nathalie Brassard; Julia Niessl; Laurie Gokool; Chantal Morrisseau; Pascale Arlotto; Cécile Tremblay; Valérie Martel-Laferrière; Andrés Finzi; Allison R Greenplate; E John Wherry; Daniel E Kaufmann

doi:10.1016/j.isci.2022.105904

An extended SARS-CoV-2 mRNA vaccine prime-boost interval enhances B cell immunity with limited impact on T cells

iScience. 2023 Jan 20;26(1):105904. doi: 10.1016/j.isci.2022.105904. Epub 2022 Dec 29.

Authors

Alexandre Nicolas^{1

2}, Gérémy Sannier^{1

2}, Mathieu Dubé¹, Manon Nayrac^{1

2}, Alexandra Tauzin^{1

2}, Mark M Painter^{3

4

5}, Rishi R Goel^{3

4}, Mélanie Laporte¹, Gabrielle Gendron-Lepage¹, Halima Medjahed¹, Justine C Williams⁵, Nathalie Brassard¹, Julia Niessl^{1

2}, Laurie Gokool¹, Chantal Morrisseau¹, Pascale Arlotto¹, Cécile Tremblay^{1

2}, Valérie Martel-Laferrière^{1

2}, Andrés Finzi^{1

2}, Allison R Greenplate^{3

4}, E John Wherry^{3

4

5}, Daniel E Kaufmann^{1

6

7}

Affiliations

¹ Centre de Recherche du CHUM, Montréal, QC H2X 0A9 Canada.
² Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC H2X 0A9, Canada.
³ Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
⁴ Immune Health®, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
⁵ Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁶ Département de Médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada.
⁷ Division of Infectious Diseases, Department of Medicine, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland.

Abstract

Spacing the first two doses of SARS-CoV-2 mRNA vaccines beyond 3-4 weeks raised initial concerns about vaccine efficacy. While studies have since shown that long-interval regimens induce robust antibody responses, their impact on B and T cell immunity is poorly known. Here, we compare SARS-CoV-2 naive donors B and T cell responses to two mRNA vaccine doses administered 3-4 versus 16 weeks apart. After boost, the longer interval results in a higher magnitude and a more mature phenotype of RBD-specific B cells. While the two geographically distinct cohorts present quantitative and qualitative differences in T cell responses at baseline and after priming, the second dose led to convergent features with overall similar magnitude, phenotype, and function of CD4⁺ and CD8⁺ T cell responses at post-boost memory time points. Therefore, compared to standard regimens, a 16-week interval has a favorable impact on the B cell compartment but minimally affects T cell immunity.

Keywords: Biological sciences; Components of the immune system; Immunology.

Abstract

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