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

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 longitu...

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Published in:	Nature medicine Vol. 27; no. 11; pp. 1990 - 2001
Main Authors:	Apostolidis, Sokratis A., Kakara, Mihir, Painter, Mark M., Goel, Rishi R., Mathew, Divij, Lenzi, Kerry, Rezk, Ayman, Patterson, Kristina R., Espinoza, Diego A., Kadri, Jessy C., Markowitz, Daniel M., E. Markowitz, Clyde, Mexhitaj, Ina, Jacobs, Dina, Babb, Allison, Betts, Michael R., Prak, Eline T. Luning, Weiskopf, Daniela, Grifoni, Alba, Lundgreen, Kendall A., Gouma, Sigrid, Sette, Alessandro, Bates, Paul, Hensley, Scott E., Greenplate, Allison R., Wherry, E. John, Li, Rui, Bar-Or, Amit
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-11-2021 Nature Publishing Group
Subjects:	631/250/1619/554 631/250/2152/2153/1291 631/250/590/2293 631/326/596/4130 692/617/375/1666 Analysis Animals Antibodies Antibodies, Monoclonal - therapeutic use Antibodies, Viral - analysis Antibodies, Viral - blood Antigens Antigens, CD20 - immunology B cells Biomedical and Life Sciences Biomedicine Cancer Research Care and treatment Case-Control Studies CD20 antigen CD4 antigen CD8 antigen Chlorocebus aethiops COVID-19 COVID-19 - prevention & control COVID-19 Vaccines - therapeutic use Decision making Diagnosis Health care Health policy HEK293 Cells Humans Immune response Immune response (humoral) Immunity, Cellular Immunity, Humoral - drug effects Immunity, Humoral - physiology Immunization Immunoglobulin G Immunological memory Immunotherapy - methods Infectious Diseases Longitudinal Studies Lymphocytes Lymphocytes B Lymphocytes T Memory cells Metabolic Diseases Molecular Medicine Monoclonal antibodies mRNA mRNA vaccines Multiple sclerosis Multiple Sclerosis - blood Multiple Sclerosis - immunology Multiple Sclerosis - therapy Neurosciences Patient outcomes Patients Priming Public health Rituximab - pharmacology Rituximab - therapeutic use RNA, Messenger - immunology RNA, Viral - immunology SARS-CoV-2 - genetics SARS-CoV-2 - immunology Severe acute respiratory syndrome coronavirus 2 Vaccination Vaccines Vero Cells Pennsylvania
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Summary:	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. SARS-CoV-2-specific antibodies and memory B cells are significantly reduced, but CD4 + and CD8 + T cells are robustly activated, in patients with multiple sclerosis on anti-CD20 monotherapy versus healthy controls after BNT162b2 or mRNA-1273 mRNA vaccination.
ISSN:	1078-8956 1546-170X
DOI:	10.1038/s41591-021-01507-2