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, G.; Nicolas, A.; Dube, M.; Marchitto, L.; Nayrac, M.; Tastet, O.; Tauzin, A.; Lima-Barbosa, R.; Laporte, M.; Cloutier, R.; Flores, A. S.; Boutin, M.; Gong, S. Y.; Benlarbi, M.; Ding, S.; Bourassa, C.; Gendron-Lepage, G.; Medjahed, H.; Goyette, G.; Brassard, N.; Ortega-Delgado, G.-G.; Niessl, J.; Gokool, L.; Morrisseau, C.; Arlotto, P.; Rios, N.; Tremblay, C.; Martel-Laferriere, V.; Prat, A.; Belair, J.; Beaubien-Souligny, W.; Goupil, R.; Nadeau-Fredette, A.-C.; Lamarche, C.; Finzi, A.; Suri, R.; Kaufmann, D. E.

doi:10.1101/2022.09.05.506622

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bioRxiv · 10.1101/2022.09.05.506622

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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Abstract

Cellular immune defects associated with suboptimal responses to SARS-CoV-2 mRNA vaccination in people receiving hemodialysis (HD) are poorly understood. We longitudinally analyzed antibody, B cell, CD4+ and CD8+ T cell vaccine responses in 27 HD patients and 26 low-risk control individuals (CI). 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 Thelper (TH) immunity. Unsupervised clustering of single-cell features reveals phenotypic and functional shifts over time and between cohorts. The third dose attenuates some features of TH cells in HD (TNF/IL-2 skewing), while others (CCR6, CXCR6, PD-1 and HLA-DR overexpression) persist. Therefore, a third vaccine dose is critical to achieve robust multifaceted immunity in hemodialysis patients, although some distinct TH characteristics endure.

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Sannier, G., Nicolas, A., Dube, M., Marchitto, L., Nayrac, M., Tastet, O., Tauzin, A., Lima-Barbosa, R., Laporte, M., Cloutier, R., Flores, A. S., Boutin, M., Gong, S. Y., Benlarbi, M., Ding, S., Bourassa, C., Gendron-Lepage, G., Medjahed, H., Goyette, G., Brassard, N., Ortega-Delgado, G.-G., Niessl, J., Gokool, L., Morrisseau, C., Arlotto, P., Rios, N., Tremblay, C., Martel-Laferriere, V., Prat, A., Belair, J., Beaubien-Souligny, W., Goupil, R., Nadeau-Fredette, A.-C., Lamarche, C., Finzi, A., Suri, R., Kaufmann, D. E.. 2022-09-07. A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+ T cell profile. https://doi.org/10.1101/2022.09.05.506622

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