Longitudinal adaptive immune responses following sequential SARS-CoV-2 vaccinations in MS patients on anti-CD20 therapies and sphingosine-1-phosphate receptor modulators

Sabatino, Joseph J.; Mittl, Kristen; Rowles, William; Zamecnik, Colin R.; Loudermilk, Rita P.; Gerungan, Chloe; Spencer, Collin M.; Sagan, Sharon A.; Alexander, Jessa; McPolin, Kira; Chen, PeiXi; Deshpande, Chinmay; Wyse, Kerri; Maiese, Eric M; Wilson, Michael R.; Zamvil, Scott S.; Bove, Riley

doi:10.1016/j.msard.2022.104484

Cited by 13 publications

(27 citation statements)

References 28 publications

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“…47 The anti-CD20 mAbs, RTX, ocrelizumab (OCR), and ofatumumab (OMB) spare the majority of antibody-secreting plasma cells but B cell depletion reduces new antibody responses to SARS-CoV-2 infection. Buffering the poor antibody response, the anti-CD20s do not appear to compromise T cell responses to SARS-CoV-2 infection in MS. [48][49][50][51] SARS-CoV-2-specific CD4 and CD8 T cell responses are detected for at least 1 year after infection, similar to healthy recovered controls. 48 COVID-19 outcomes in patients treated with anti-CD20 mAbs have varied.…”

Section: Assay (References) Function/methods Notesmentioning

confidence: 96%

“…[49][50][51]64 However, with OMB, a third booster vaccination can mitigate the decreased antibody responses and allow elevation of titers. [49][50][51] In addition, SARS-CoV-2-specific T cell responses after full-course vaccination can occur in patients treated with anti-CD20 therapy (Supplementary Table 1). SARS-CoV-2-specific memory T cell responses are comparable in BNT162b2-vaccinated healthy controls, untreated patients with MS, and OCR-treated patients with MS when assessed 4.3 months (median) after last DMT treatment.…”

Section: Assay (References) Function/methods Notesmentioning

confidence: 99%

“…53 With mRNA COVID-19 vaccination, T cell and humoral responses of patients with MS may vary between treatments (Supplementary Table 1; Figure 1). [49][50][51][54][55][56][57][58][59][60][61][62][63] Patients treated with B cell-depleting anti-CD20 therapy have lower antibody responses to mRNA COVID-19 vaccines, for months after the last anti-CD20 treatment. [49][50][51]64 However, with OMB, a third booster vaccination can mitigate the decreased antibody responses and allow elevation of titers.…”

Section: Assay (References) Function/methods Notesmentioning

confidence: 99%

“…[49][50][51][54][55][56][57][58][59][60][61][62][63] Patients treated with B cell-depleting anti-CD20 therapy have lower antibody responses to mRNA COVID-19 vaccines, for months after the last anti-CD20 treatment. [49][50][51]64 However, with OMB, a third booster vaccination can mitigate the decreased antibody responses and allow elevation of titers. [49][50][51] In addition, SARS-CoV-2-specific T cell responses after full-course vaccination can occur in patients treated with anti-CD20 therapy (Supplementary Table 1).…”

Section: Assay (References) Function/methods Notesmentioning

confidence: 99%

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T cell responses to COVID-19 infection and vaccination in patients with multiple sclerosis receiving disease-modifying therapy

et al. 2022

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Background: Multiple sclerosis (MS) is a neurological disorder marked by accumulating immune-mediated damage to the central nervous system. The dysregulated immune system in MS combined with immune effects of disease-modifying therapies (DMTs) used in MS treatment could alter responses to infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). Most of the literature on immune response to SARS-CoV-2 infection and COVID-19 vaccination, in both the general population and patients with MS on DMTs, has focused on humoral immunity. However, immune response to COVID-19 involves multiple lines of defense, including T cells. Objective and Methods: We review innate and adaptive immunity to COVID-19 and expand on the role of T cells in mediating protective immunity against SARS-CoV-2 infection and in responses to COVID-19 vaccination in MS. Results: Innate, humoral, and T cell immune responses combat COVID-19 and generate protective immunity. Assays detecting cytokine expression by T cells show an association between SARS-CoV-2-specific T cell responses and milder/asymptomatic COVID-19 and protective immune memory. Conclusion: Studies of COVID-19 immunity in people with MS on DMTs should ideally include comprehensive assessment of innate, humoral, and T cell responses.

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Section: Assay (References) Function/methods Notesmentioning

confidence: 96%

Section: Assay (References) Function/methods Notesmentioning

confidence: 99%

Section: Assay (References) Function/methods Notesmentioning

confidence: 99%

Section: Assay (References) Function/methods Notesmentioning

confidence: 99%

See 2 more Smart Citations

T cell responses to COVID-19 infection and vaccination in patients with multiple sclerosis receiving disease-modifying therapy

et al. 2022

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“…In that study, the third vaccination increased IgG titers by a factor of 1.4 to 1.6 compared to titers after the second vaccination. This study also suggests that after three vaccinations, during ofatumumab treatment, B-cell and T-cell responses were still lower than among healthy controls and compared to patients who received two or three doses of vaccine before ofatumumab was started [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Results on SARS-CoV-2 mRNA Vaccine Booster from an Open-Label Multicenter Study in Ofatumumab-Treated Participants with Relapsing Multiple Sclerosis

et al. 2023

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Background: Few data exist on how ofatumumab treatment impacts SARS-CoV-2 booster vaccination response. Methods: KYRIOS is an ongoing prospective open-label multicenter study on the response to initial and booster SARS-CoV-2 mRNA vaccination before or during ofatumumab treatment in relapsing MS patients. The results on the initial vaccination cohort have been published previously. Here, we describe 23 patients who received their initial vaccination outside of the study but booster vaccination during the study. Additionally, we report the booster results of two patients in the initial vaccination cohort. The primary endpoint was SARS-CoV-2-specific T-cell response at month 1. Furthermore, serum total and neutralizing antibodies were measured. Results: The primary endpoint was reached by 87.5% of patients with booster before (booster cohort 1, N = 8) and 46.7% of patients with booster during ofatumumab treatment (booster cohort 2, N = 15). Seroconversion rates for neutralizing antibodies increased from 87.5% at baseline to 100.0% at month 1 in booster cohort 1 and from 71.4% to 93.3% in booster cohort 2. Of note, 3 of 4 initially seronegative patients in booster cohort 2 and one seronegative patient in the initial vaccination cohort seroconverted after the booster during ofatumumab treatment. Conclusions: Booster vaccinations increase neutralizing antibody titers in ofatumumab-treated patients. A booster is recommended in ofatumumab-treated patients.

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Longitudinal study of immunity to SARS‐CoV2 in ocrelizumab‐treated MS patients up to 2 years after COVID‐19 vaccination

Kister,

Curtin,

Piquet

et al. 2024

Ann Clin Transl Neurol

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Objectives(1) To plot the trajectory of humoral and cellular immune responses to the primary (two‐dose) COVID‐19 mRNA series and the third/booster dose in B‐cell‐depleted multiple sclerosis (MS) patients up to 2 years post‐vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID‐19 infections on SARS CoV‐2‐specific immunity.MethodsSixty ocrelizumab‐treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre‐vaccination, and then 4, 12, 24, and 48 weeks post‐primary series, and 4, 12, 24, and 48 weeks post‐booster. Binding anti‐Spike antibody responses were assessed with multiplex bead‐based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live‐virus immunofluorescence‐based microneutralization assay. Spike‐specific cellular responses were assessed with IFNγ/IL‐2 ELISpot (Invitrogen) and, in a subset, by sequencing complementarity determining regions (CDR)‐3 within T‐cell receptors (Adaptive Biotechnologies). A linear mixed‐effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses.ResultsThe primary vaccination induced an 11‐ to 208‐fold increase in binding and neutralizing antibody levels and a 3‐ to 4‐fold increase in IFNγ/IL‐2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3‐ to 5‐fold increase in binding antibodies and 4‐ to 5‐fold increase in IFNγ/IL‐2, which were maintained for up to 1 year. Infections had a variable impact on immunity.InterpretationHumoral and cellular benefits of COVID‐19 vaccination in B‐cell‐depleted MS patients were sustained for up to 2 years when booster doses were administered.

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Longitudinal adaptive immune responses following sequential SARS-CoV-2 vaccinations in MS patients on anti-CD20 therapies and sphingosine-1-phosphate receptor modulators

Cited by 13 publications

References 28 publications

T cell responses to COVID-19 infection and vaccination in patients with multiple sclerosis receiving disease-modifying therapy

T cell responses to COVID-19 infection and vaccination in patients with multiple sclerosis receiving disease-modifying therapy

Results on SARS-CoV-2 mRNA Vaccine Booster from an Open-Label Multicenter Study in Ofatumumab-Treated Participants with Relapsing Multiple Sclerosis

Longitudinal study of immunity to SARS‐CoV2 in ocrelizumab‐treated MS patients up to 2 years after COVID‐19 vaccination

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