Dataset Information

Preserved T-cell response in anti-CD20-treated multiple sclerosis patients following SARS-CoV-2 vaccination.

ABSTRACT:

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has tremendous implications for the management of patients with autoimmune conditions such as multiple sclerosis (MS) under immune therapies targeting CD20⁺ B cells (aCD20).

Objectives

Here, we investigated humoral and cellular immune responses, including anti-spike titers, neutralization against SARS-CoV-2 wild-type (WT), delta, and omicron variant and T cell responses of aCD20-treated relapsing-remitting MS patients following SARS-CoV-2 vaccination compared with healthy controls.

Methods

Blood samples were collected within 4-8 weeks following the second vaccination against SARS-CoV-2. Sera were analyzed for anti-SARS-CoV-2 spike antibodies and neutralization capacity against pseudovirus for wild-type (WT), delta, and omicron variant. Peripheral blood mononuclear cells (PBMCs) were stimulated with a SARS-CoV-2 peptide pool and analyzed via flow cytometry.

Results

The aCD20-treated MS patients had lower anti-SARS-CoV-2-spike titers, which correlated with B cell repopulation. Sera of aCD20-treated patients had reduced capacity to neutralize WT, delta, and omicron pseudoviruses in vitro. On the contrary, PBMCs of aCD20-treated patients elicited higher frequencies of CD3⁺ T cells and CD4⁺ T cells and comparable response of cytotoxic T cells, while Th1 response was reduced following restimulation with SARS-CoV-2.

Conclusion

In summary, aCD20-treated patients have a reduced humoral immune response, depending on B cell repopulation, in accordance with preserved cellular immune response, suggesting partial cellular protection against SARS-CoV-2.

SUBMITTER: Faissner S

PROVIDER: S-EPMC9742512 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Preserved T-cell response in anti-CD20-treated multiple sclerosis patients following SARS-CoV-2 vaccination.

Faissner Simon S Heitmann Neele N Rohling Ricarda R Ceylan Ulas U Bongert Marielena M Plaza-Sirvent Carlos C Marheinecke Corinna C Pedreiturria Xiomara X Ayzenberg Ilya I Hellwig Kerstin K Schmitz Ingo I Pfaender Stephanie S Gold Ralf R

Therapeutic advances in neurological disorders 20221209

<h4>Background</h4>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has tremendous implications for the management of patients with autoimmune conditions such as multiple sclerosis (MS) under immune therapies targeting CD20<sup>+</sup> B cells (aCD20).<h4>Objectives</h4>Here, we investigated humoral and cellular immune responses, including anti-spike titers, neutralization against SARS-CoV-2 wild-type (WT), delta, and omicron variant and T cell responses of aCD20-treated ...[more]

PMID: 36518553

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Project description:BackgroundSphingosine-1-phosphate receptor (S1P) modulators and anti-CD20 therapies impair humoral responses to SARS-CoV-2 mRNA vaccines. Relatively few studies have assessed the impact of an array of disease modifying therapies (DMTs) for multiple sclerosis (MS) on T cell immune responses to SARS-CoV-2 vaccination.MethodsIn 101 people with MS, we measured humoral responses via an immunoassay to measure IgG against the COVID-19 spike S1 glycoprotein in serum. We also measured T cell responses using FluoroSpot assay for interferon gamma (IFN-γ) (Mabtech, Sweden) using cryopreserved rested PBMCs and then incubated in cRPMI with 1µg/ml of pooled peptides spanning the entire spike glycoprotein (Genscript, 2 pools; 158 peptides each). Plates were read on an AID iSpot Spectrum to determine the number of spot forming cells (SFC)/106 PBMCs. We tested for differences in immune responses across DMTs using linear models.FindingsHumoral responses were detected in 22/39 (56.4%) participants on anti-CD20 and in 59/63 (93.6%) participants on no or other DMTs. In a subset (n=88; 87%), T cell responses were detected in 76/88 (86%), including 32/33 (96.9%) participants on anti-CD20 therapies. Anti-CD20 therapies were associated with an increase in IFN-γ SFC counts relative to those on no DMT or other DMTs (for anti-CD20 vs. no DMT: 425.9% higher [95%CI: 109.6%, 1206.6%] higher; p<0.001; for anti-CD20 vs. other DMTs: 289.6% [95%CI: 85.9%, 716.6%] higher; p<0.001).InterpretationWe identified a robust T cell response in individuals on anti-CD20 therapies despite a reduced humoral response to SARS-CoV-2 vaccination. Follow up studies are needed to determine if this translates to protection against COVID-19 infection.FundingThis study was funded partially by 1K01MH121582-01 from NIH/NIMH and TA-1805-31136 from the National MS Society (NMSS) to KCF and TA-1503-03465 and JF-2007-37655 from the NMSS to PB. This study was also supported through the generosity of the collective community of donors to the Johns Hopkins University School of Medicine for COVID research.

Dataset Information

Preserved T-cell response in anti-CD20-treated multiple sclerosis patients following SARS-CoV-2 vaccination.

Background

Objectives

Methods

Results

Conclusion

Publications

Preserved T-cell response in anti-CD20-treated multiple sclerosis patients following SARS-CoV-2 vaccination.

Similar Datasets

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