Dataset Information

Humoral and cellular immune responses to SARS CoV-2 vaccination in People with Multiple Sclerosis and NMOSD patients receiving immunomodulatory treatments.

ABSTRACT:

Background

Vaccination against SARS CoV-2 results in excellent personal protection against a severe course of COVID19. In People with Multiple Sclerosis (PwMS) vaccination efficacy may be reduced by immunomodulatory medications.

Objective

To assess the vaccination induced cellular and humoral immune response in PwMS receiving disease modifying therapies.

Methods

In a monocentric observational study on PwMS and patients with Neuromyelitis optica we quantified the cellular and humoral immune responses to SARS CoV-2.

Results

PwMS receiving glatiramer acetate, Interferon-ß, Dimethylfumarate, Cladribine or Natalizumab had intact humoral and cellular immune responses following vaccination against SARS CoV-2. B-cell depleting therapies reduced B-cell responses but did not affect T cell responses. Sphingosin-1-Phospate (S1P) inhibitors strongly reduced humoral and cellular immune responses. There was a good agreement between the Interferon gamma release assay and the T-SPOT assay used to measure viral antigen induced T-cell responses.

Conclusion

This study demonstrates that S1P inhibitors impair the cellular and humoral immune response in SARS CoV-2 vaccination, whereas patients receiving B-cell depleting therapies mount an intact cellular immune response. These data can support clinicians in counselling their PwMS and NMOSD patients during the COVID 19 pandemic.

SUBMITTER: Bock H

PROVIDER: S-EPMC8783535 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Humoral and cellular immune responses to SARS CoV-2 vaccination in People with Multiple Sclerosis and NMOSD patients receiving immunomodulatory treatments.

Bock H H Juretzek T T Handreka R R Ruhnau J J Löbel M M Reuner K K Peltroche H H Dressel A A

Multiple sclerosis and related disorders 20220122

<h4>Background</h4>Vaccination against SARS CoV-2 results in excellent personal protection against a severe course of COVID19. In People with Multiple Sclerosis (PwMS) vaccination efficacy may be reduced by immunomodulatory medications.<h4>Objective</h4>To assess the vaccination induced cellular and humoral immune response in PwMS receiving disease modifying therapies.<h4>Methods</h4>In a monocentric observational study on PwMS and patients with Neuromyelitis optica we quantified the cellular an ...[more]

PMID: 35180617

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Project description:ObjectiveSARS-CoV-2 vaccinations have demonstrated vaccine-immunogenicity in healthy volunteers, however, efficacy in immunosuppressed patients is less well characterised. There is an urgent need to address the impact of immunosuppression on vaccine immunogenicity.MethodsSerological, T-cell ELISpot, cytokines and immunophenotyping were used to assess vaccine responses (either BNT162b2 mRNA or ChAdOx1 nCoV-19) in double-vaccinated patients receiving immunosuppression for renal transplants or haematological malignancies (n = 13). Immunological responses in immunosuppressed patients (VACC-IS) were compared to immunocompetent vaccinated (VACC-IC, n = 12), unvaccinated (UNVACC, n = 11) and infection-naïve unvaccinated (HC, n = 3) cohorts.ResultsNo significant different differences in T-cell responses were observed between VACC-IS and VACC-IC (92%) to spike-peptide (S) stimulation. UNVACC had the highest T-cell non-responders (n = 3), whereas VACC-IC and VACC-IS both had one T-cell non-responder. No significant differences in humoral responses were observed between VACC-IC and VACC-IS, with 92% (12/13) of VACC-IS patients demonstrating seropositivity. One VACC-IS failed to seroconvert, however had detectable T-cell responses. All VACC-IC participants were seropositive for anti-spike antibodies. VACC-IS and VACC-IC participants elicited strong Th1 cytokine response with immunodominance towards S-peptide. Differences in T-cell immunophenotyping were seen between VACC-IS and VACC-IC, with lower CD8+ activation and T-effector memory phenotype observed in VACC-IS.ConclusionSARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppressive therapy, with responses comparable to vaccinated immunocompetent participants. Lower humoral responses were seen in patients treated with B-cell depleting therapeutics, but with preserved T-cell responses. We suggest further work to correlate both protective immunity and longevity of these responses in both healthy and immunosuppressed patients.

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

Humoral and cellular immune responses to SARS CoV-2 vaccination in People with Multiple Sclerosis and NMOSD patients receiving immunomodulatory treatments.

Background

Objective

Methods

Results

Conclusion

Publications

Humoral and cellular immune responses to SARS CoV-2 vaccination in People with Multiple Sclerosis and NMOSD patients receiving immunomodulatory treatments.

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