Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients.

Autor:	Becker M; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany., Cossmann A; Department for Rheumatology and Immunology, Hannover Medical School, Hannover, Germany., Lürken K; Department of Internal Medicine and Nephrology, Dialysis Centre Eickenhof, Langenhagen, Germany., Junker D; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany., Gruber J; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany., Juengling J; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany., Ramos GM; Department for Rheumatology and Immunology, Hannover Medical School, Hannover, Germany., Beigel A; Department of Internal Medicine and Nephrology, Dialysis Centre Eickenhof, Langenhagen, Germany., Wrenger E; Department of Internal Medicine and Nephrology, Dialysis Centre Eickenhof, Langenhagen, Germany., Lonnemann G; Department of Internal Medicine and Nephrology, Dialysis Centre Eickenhof, Langenhagen, Germany., Stankov MV; Department for Rheumatology and Immunology, Hannover Medical School, Hannover, Germany., Dopfer-Jablonka A; Department for Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.; German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Hannover, Germany., Kaiser PD; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany., Traenkle B; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany., Rothbauer U; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.; Pharmaceutical Biotechnology, University of Tübingen, Tübingen, Germany., Krause G; German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Hannover, Germany.; Department Epidemiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.; TWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany., Schneiderhan-Marra N; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany., Strengert M; Department Epidemiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.; TWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany., Dulovic A; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany., Behrens GMN; Department for Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.; German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Hannover, Germany.; CiiM - Centre for Individualized Infection Medicine, Hannover, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Oct 06; Vol. 13, pp. 1004045. Date of Electronic Publication: 2022 Oct 06 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.1004045
Abstrakt:	Haemodialysis patients respond poorly to vaccination and continue to be at-risk for severe COVID-19. Therefore, dialysis patients were among the first for which a fourth COVID-19 vaccination was recommended. However, targeted information on how to best maintain immune protection after SARS-CoV-2 vaccinations in at-risk groups for severe COVID-19 remains limited. We provide, to the best of our knowledge, for the first time longitudinal vaccination response data in dialysis patients and controls after a triple BNT162b2 vaccination and in the latter after a subsequent fourth full-dose of mRNA-1273. We analysed systemic and mucosal humoral IgG responses against the receptor-binding domain (RBD) and ACE2-binding inhibition towards variants of concern including Omicron and Delta with multiplex-based immunoassays. In addition, we assessed Spike S1-specific T-cell responses by interferon γ release assay. After triple BNT162b2 vaccination, anti-RBD B.1 IgG and ACE2 binding inhibition reached peak levels in dialysis patients, but remained inferior compared to controls. Whilst we detected B.1-specific ACE2 binding inhibition in 84% of dialysis patients after three BNT162b2 doses, binding inhibition towards the Omicron variant was only detectable in 38% of samples and declining to 16% before the fourth vaccination. By using mRNA-1273 as fourth dose, humoral immunity against all SARS-CoV-2 variants tested was strongly augmented with 80% of dialysis patients having Omicron-specific ACE2 binding inhibition. Modest declines in T-cell responses in dialysis patients and controls after the second vaccination were restored by the third BNT162b2 dose and significantly increased by the fourth vaccination. Our data support current advice for a four-dose COVID-19 immunisation scheme for at-risk individuals such as haemodialysis patients. We conclude that administration of a fourth full-dose of mRNA-1273 as part of a mixed mRNA vaccination scheme to boost immunity and to prevent severe COVID-19 could also be beneficial in other immune impaired individuals. Additionally, strategic application of such mixed vaccine regimens may be an immediate response against SARS-CoV-2 variants with increased immune evasion potential. Competing Interests: NS-M was a speaker at Luminex user meetings in the past. The Natural and Medical Sciences Institute at the University of Tübingen is involved in applied research projects as a fee for services with the Luminex Corporation. GMNB was a speaker on a symposium sponsored by Moderna. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Becker, Cossmann, Lürken, Junker, Gruber, Juengling, Ramos, Beigel, Wrenger, Lonnemann, Stankov, Dopfer-Jablonka, Kaiser, Traenkle, Rothbauer, Krause, Schneiderhan-Marra, Strengert, Dulovic and Behrens.)
Databáze:	MEDLINE
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