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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                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200920) compared with healthy controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910) 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\n                    <jats:sub>FH<\/jats:sub>\n                    ) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (T\n                    <jats:sub>H<\/jats:sub>\n                    1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating T\n                    <jats:sub>FH<\/jats:sub>\n                    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.\n                  <\/jats:p>","DOI":"10.1038\/s41591-021-01507-2","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T06:03:16Z","timestamp":1631599396000},"page":"1990-2001","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":469,"title":["Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0224-0097","authenticated-orcid":false,"given":"Sokratis A.","family":"Apostolidis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihir","family":"Kakara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0180-2748","authenticated-orcid":false,"given":"Mark M.","family":"Painter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishi R.","family":"Goel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8323-7358","authenticated-orcid":false,"given":"Divij","family":"Mathew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry","family":"Lenzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"Rezk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina R.","family":"Patterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9627-6508","authenticated-orcid":false,"given":"Diego A.","family":"Espinoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessy C.","family":"Kadri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Markowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clyde","family":"E. 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E.J.W. is consulting or is an advisor for Merck, Marengo, Janssen, Related Sciences, Synthekine and Surface Oncology; is a founder of Danger Bio, Surface Oncology and Arsenal Biosciences; and is an inventor on a patent (US patent no. US10370446B2) submitted by Emory University that covers the use of PD-1 blockade to treat infections and cancer. A.S. is a consultant for Gritstone, Flow Pharma, CellCarta, Arcturus Therapeutics, Oxford Immunotec and Avalia Immunotherapies. La Jolla Institute for Immunology has filed for patent protection for various aspects of T cell epitope and vaccine design work. E.T.L.P. is consulting or is an advisor for Roche Diagnostics, ENPICOM, The Antibody Society, Immune Epitope Database and the American Autoimmune Related Diseases Association. D.J. is on the Biogen, Genentech, Novartis, EMD Serono, Banner Life Sciences, Bristol Myers Squibb and Sanofi-Genzyme advisory boards and has received research support (clinical trial site principal investigator) from Biogen, Genentech and University of California, Los Angeles. A.B.O. has participated as a speaker in meetings sponsored by and received consulting fees and\/or grant support from Accure Therapeutics, Atara Biotherapeutics, Biogen, Bristol Myers Squibb\/Celgene\/Receptos, GlaxoSmithKline, Gossamer Bio, Janssen\/Actelion, MedImmune, Merck\/EMD Serono, Novartis, Roche\/Genentech and Sanofi-Genzyme. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}