Altered cellular immune response to vaccination against SARS-CoV-2 in patients suffering from autoimmunity with B-cell depleting therapy

Abstract

B-cell depleting therapies result in diminished humoral immunity following vaccination against COVID-19, but our understanding on the impact on cellular immune responses is limited. Here, we performed a detailed analysis of cellular immunity following mRNA vaccination in patients receiving B-cell depleting therapy using ELISpot assay and flow cytometry. Anti-SARS-CoV-2 spike receptor-binding domain antibody assays were performed to elucidate B-cell responses. To complement our cellular analysis, we performed immunophenotyping for T- and B-cell subsets. We show that SARS-CoV-2 vaccination using mRNA vaccines elicits cellular T-cell responses in patients under B-cell depleting therapy. Some facets of this immune response including TNFα production of CD4⁺ T-cells and granzyme B production of CD8⁺ T-cells, however, are distinctly diminished in these patients. Consequently, it appears that the finely coordinated process of T-cell activation with a uniform involvement of CD4⁺ and CD8⁺ T-cells as seen in HCs is disturbed in autoimmune patients. In addition, we observed that immune cell composition does impact cellular immunity as well as sustainability of anti-spike antibody titers. Our data suggest disturbed cellular immunity following mRNA vaccination in patients treated with B-cell depleting therapy. Immune cell composition may be an important determinant for vaccination efficacy.

Keywords: Autoimmunity; Covid-19; Ocrelizumab; Rituximab; T-cells; Vaccination.