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

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.

SUBMITTER: Sannier G

PROVIDER: S-EPMC9902290 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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

Sannier Gérémy G Nicolas Alexandre A Dubé Mathieu M Marchitto Lorie L Nayrac Manon M Tastet Olivier O Chatterjee Debashree D Tauzin Alexandra A Lima-Barbosa Raphaël R Laporte Mélanie M Cloutier Rose R Sreng Flores Alina M AM Boutin Marianne M Gong Shang Yu SY Benlarbi Mehdi M Ding Shilei S Bourassa Catherine C Gendron-Lepage Gabrielle G Medjahed Halima H Goyette Guillaume G Brassard Nathalie N Delgado Gloria-Gabrielle GG Niessl Julia J Gokool Laurie L Morrisseau Chantal C Arlotto Pascale P Rios Norka N Tremblay Cécile C Martel-Laferrière Valérie V Prat Alexandre A Bélair Justin J Beaubien-Souligny William W Goupil Rémi R Nadeau-Fredette Annie-Claire AC Lamarche Caroline C Finzi Andrés A Suri Rita S RS Kaufmann Daniel E DE

Cell reports. Medicine 20230207 3

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 respo ...[more]

PMID: 36863335

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Project description:Most patients with end-stage kidney disease value their health-related quality of life (HRQoL) and want to know how it will be affected by their dialysis modality. We extended the findings of two prior clinical trial reports to estimate the effects of frequent compared to conventional hemodialysis on additional measures of HRQoL. The Daily Trial randomly assigned 245 patients to receive frequent (six times per week) or conventional (three times per week) in-center hemodialysis. The Nocturnal Trial randomly assigned 87 patients to receive frequent nocturnal (six times per week) or conventional (three times per week) home hemodialysis. All patients were on conventional hemodialysis prior to randomization, with an average feeling thermometer score of 70 to 75 (a visual analog scale from 0 to 100 where 100 is perfect health), an average general health scale score of 40 to 47 (a score from 0 to 100 where 100 is perfect health), and an average dialysis session recovery time of 2 to 3 hours. Outcomes are reported as the between-treatment group differences in one-year change in HRQoL measures and analyzed using linear mixed effects models. After one year in the Daily Trial, patients assigned to frequent in-center hemodialysis reported a higher feeling thermometer score, better general health, and a shorter recovery time after a dialysis session compared to standard thrice-weekly dialysis. After one year in the Nocturnal Trial, patients assigned to frequent home hemodialysis also reported a shorter recovery time after a dialysis session, but no statistical difference in their feeling thermometer or general health scores compared to standard home dialysis schedules. Thus, patients receiving day or nocturnal hemodialysis on average recovered approximately one hour earlier from a frequent compared to conventional hemodialysis session. Patients treated in an in-center dialysis facility reported better HRQoL with frequent compared to conventional hemodialysis.

Dataset Information

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

Publications

A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4<sup>+</sup> T cell profile.

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