Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy.

Autor: Apostolidis SA; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Division of Rheumatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Immune Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Kakara M; Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Painter MM; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Immune Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Goel RR; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Immune Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Mathew D; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Immune Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Lenzi K; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Rezk A; Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Patterson KR; Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Espinoza DA; Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Immunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Kadri JC; Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Markowitz DM; Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., E Markowitz C; Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Mexhitaj I; Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Jacobs D; Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Babb A; Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Betts MR; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Prak ETL; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Weiskopf D; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA., Grifoni A; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA., Lundgreen KA; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Penn Center for Research on Coronavirus and Other Emerging Pathogens, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Gouma S; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Sette A; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA, USA.; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA, USA., Bates P; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Penn Center for Research on Coronavirus and Other Emerging Pathogens, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Hensley SE; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Greenplate AR; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Immune Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Wherry EJ; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. wherry@pennmedicine.upenn.edu.; Immune Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. wherry@pennmedicine.upenn.edu.; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. wherry@pennmedicine.upenn.edu.; Parker Institute for Cancer Immunotherapy, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. wherry@pennmedicine.upenn.edu., Li R; Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. lirui158@pennmedicine.upenn.edu.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. lirui158@pennmedicine.upenn.edu., Bar-Or A; Center for Neuroinflammation and Experimental Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. amitbar@pennmedicine.upenn.edu.; Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. amitbar@pennmedicine.upenn.edu.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2021 Nov; Vol. 27 (11), pp. 1990-2001. Date of Electronic Publication: 2021 Sep 14.
DOI: 10.1038/s41591-021-01507-2
Abstrakt: SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (T FH ) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T H 1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T FH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.
(© 2021. The Author(s).)
Databáze: MEDLINE
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