AUTHOR=Groß-Albenhausen Elina , Weier Alicia , Velten Markus , Heider Thorsten , Chunder Rittika , Kuerten Stefanie 

TITLE=Immune monitoring of SARS-CoV-2-specific T cell and B cell responses in patients with multiple sclerosis treated with ocrelizumab

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1254128

DOI=10.3389/fimmu.2023.1254128

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Since the development of the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there has been significant interest in determining the effectiveness of SARS-CoV-2 vaccines in patients under immunomodulatory or immunosuppressive therapies. The aim of this study was to evaluate the impact of ocrelizumab, a monoclonal anti-CD20 antibody, on SARS-CoV-2-specific T cell and B cell responses in patients with relapsing-remitting multiple sclerosis (RRMS).</p></sec><sec><title>Methods</title><p>To this end, peripheral blood mononuclear cells (PBMCs) were isolated from <italic>n</italic> = 23 patients with RRMS. Of these patients, <italic>n</italic> = 17 were tested before (time point t<sub>0</sub>) and one month after (time point t<sub>1</sub>) their first dose of ocrelizumab. In addition, we studied <italic>n</italic> = 9 RRMS patients that got infected with SARS-CoV-2 over the course of ocrelizumab therapy (time point t<sub>2</sub>). PBMCs were also isolated from <italic>n</italic> = 19 age- and gender-matched healthy controls (HCs) after vaccination or infection with SARS-CoV-2, respectively. Interferon-γ (IFN-γ)/interleukin-2 (IL-2) and granzyme B (GzB)/perforin (PFN) double-color enzyme-linked immunospot (ELISPOT) assays or single-color ELISPOT assays were performed to measure SARS-CoV-2 antigen-specific T cell and B cell responses. Anti-viral antibody titers were quantified in the serum by chemiluminescence immunoassay.</p></sec><sec><title>Results</title><p>Our data indicate a significant difference in the SARS-CoV-2 specific IFN-γ (<italic>P</italic> = 0.0119) and PFN (<italic>P</italic> = 0.0005) secreting T cell compartment in the MS cohort at t<sub>0</sub> compared to HCs. Following the first dose of ocrelizumab treatment, a significant decrease in the number of SARS-CoV-2 spike protein-specific B cells was observed (<italic>P</italic> = 0.0012). Infection with SARS-CoV-2 in MS patients under ocrelizumab therapy did not significantly alter their existing immune response against the virus. Kaplan-Meier survival analysis suggested that the spike S1 protein-specific immunoglobulin (Ig)G response might be a key parameter for predicting the probability of (re)infection with SARS-CoV-2.</p></sec><sec><title>Discussion</title><p>Our results call for a critical discussion regarding appropriate vaccination intervals and potential biomarkers for the prediction of (re)infection with SARS-CoV-2 in patients with MS receiving ocrelizumab.</p></sec><sec><title>Unique identifier</title><p>DRKS00029110; URL: <ext-link ext-link-type="uri" xlink:href="http://apps.who.int/trialsearch/" xmlns:xlink="http://www.w3.org/1999/xlink">http://apps.who.int/trialsearch/</ext-link>.</p></sec>