Cell Rep Med . A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+ T cell profile

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Cell Rep Med


. 2023 Feb 7;100955.
doi: 10.1016/j.xcrm.2023.100955. Online ahead of print.
A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4⁺ T cell profile


Gérémy Sannier ¹ , Alexandre Nicolas ¹ , Mathieu Dubé ² , Lorie Marchitto ¹ , Manon Nayrac ¹ , Olivier Tastet ² , Debashree Chatterjee ¹ , Alexandra Tauzin ¹ , Raphaël Lima-Barbosa ³ , Mélanie Laporte ² , Rose Cloutier ² , Alina M Sreng Flores ² , Marianne Boutin ¹ , Shang Yu Gong ⁴ , Mehdi Benlarbi ¹ , Shilei Ding ² , Catherine Bourassa ² , Gabrielle Gendron-Lepage ² , Halima Medjahed ² , Guillaume Goyette ² , Nathalie Brassard ² , Gloria-Gabrielle Delgado ² , Julia Niessl ¹ , Laurie Gokool ² , Chantal Morrisseau ² , Pascale Arlotto ² , Norka Rios ⁵ , Cécile Tremblay ¹ , Valérie Martel-Laferrière ¹ , Alexandre Prat ⁶ , Justin Bélair ³ , William Beaubien-Souligny ⁷ , Rémi Goupil ⁸ , Annie-Claire Nadeau-Fredette ⁹ , Caroline Lamarche ⁹ , Andrés Finzi ¹⁰ , Rita S Suri ¹¹ , Daniel E Kaufmann ¹²



Affiliations

• PMID: 36863335
• DOI: 10.1016/j.xcrm.2023.100955

Abstract

Cellular immune defects associated with suboptimal responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in people receiving hemodialysis (HD) are poorly understood. We longitudinally analyze antibody, B cell, CD4⁺, and CD8⁺ T cell vaccine responses in 27 HD patients and 26 low-risk control individuals (CIs). The first two doses elicit weaker B cell and CD8⁺ T cell responses in HD than in CI, while CD4⁺ T cell responses are quantitatively similar. In HD, a third dose robustly boosts B cell responses, leads to convergent CD8⁺ T cell responses, and enhances comparatively more T helper (T_H) immunity. Unsupervised clustering of single-cell features reveals phenotypic and functional shifts over time and between cohorts. The third dose attenuates some features of T_H cells in HD (tumor necrosis factor alpha [TNFα]/interleukin [IL]-2 skewing), while others (CCR6, CXCR6, programmed cell death protein 1 [PD-1], and HLA-DR overexpression) persist. Therefore, a third vaccine dose is critical to achieving robust multifaceted immunity in hemodialysis patients, although some distinct T_H characteristics endure.

Keywords: B cell immunity; COVID-19; Hemodialysis; Immune cell phenotyping; SARS-CoV-2; T cell immunity; Vaccine response; mRNA vaccine.