Journal Article

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

Kakara, Mihir, Apostolidis, Sokratis A., Painter, Mark M., Weiskopf, Daniela, Goel, Rishi R., Espinoza, Diego A., Sette, Alessandro, Wherry, E. John, Jacobs, Dina, Markowitz, Daniel M., Grifoni, Alba, Hensley, Scott E., E. Markowitz, Clyde, Babb, Allison, Gouma, Sigrid, Lenzi, Kerry, Bar-Or, Amit, Rezk, Ayman, Patterson, Kristina R., Kadri, Jessy C., Lundgreen, Kendall A., Mexhitaj, Ina, Betts, Michael R., Bates, Paul, Prak, Eline T. Luning, Li, Rui, Greenplate, Allison R., Mathew, Divij

2021

Overview

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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 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