Humoral Immune Response after the Third SARS-CoV-2 mRNA Vaccination in CD20 Depleted People with Multiple Sclerosis.

Lutz Achtnichts,Oliver Findling,Krassen Nedeltchev,Johann Sellner,Barbara Jakopp,Christoph Andreas Fux,Michael Oberle

doi:10.3390/vaccines9121470

Lutz Achtnichts, Oliver Findling + Show 5 more

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https://doi.org/10.3390/vaccines9121470

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Abstract

CD20 depletion is a risk factor for unfavorable outcomes of COVID-19 in people with MS (pwMS). Evidence suggests that protective IgG response to mRNA-based vaccines in B cell-depleted individuals is limited. We studied the seroconversion after the third mRNA SARS-CoV-2 vaccine in B cell-depleted pwMS with limited or no IgG response after the standard immunization. Sixteen pwMS treated with ocrelizumab or rituximab received a third homologous SARS-CoV-2 mRNA vaccine, either the Moderna mRNA-1273 or Pfizer-BioNTech’s BNT162b2 vaccine. We quantified the response of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 four weeks later. An antibody titer of 100 AU/mL or more was considered clinically relevant. The median time between the last infusion of the anti-CD20 treatment and the third vaccination was 22.9 weeks (range 15.1–31.3). After the third vaccination, one out of 16 patients showed an IgG titer deemed clinically relevant. Only the seroconverted patient had measurable B-cell counts at the time of the third vaccination. The development of a humoral immune response remains rare in pwMS on anti-CD20 therapy, even after third dose of the homologous SARS-CoV-2 mRNA vaccine. It remains to be determined whether T-cell responses can compensate for the lack of seroconversion and provide sufficient protection against CoV-2 infections.

Highlights

Coronavirus infectious disease 2019 (COVID-19), a multi-organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to take its toll on health, medical care, and economy [1]
We offered a third vaccination if the antibody response was insufficient and measured the titer again four weeks later
We identified 51 people with MS (pwMS) treated with OCR or RTX who underwent antibody detection at least four weeks after a second dose of the mRNA-1273 or BNT162b2 vaccines and had no history of COVID-19 infection

Summary

Introduction

Coronavirus infectious disease 2019 (COVID-19), a multi-organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to take its toll on health, medical care, and economy [1]. The mRNA-based BNT162b2 (Pfizer– BioNTech, BioNTech Manufacturing GmbH, 55131 Mainz, Germany) and mRNA-1273 (Moderna Biotech Spain, S.L., 28010 Madrid, Spain) vaccines proved efficacious in phase 3 trials and were the only licensed vaccines against SARS-CoV-2 in Switzerland until October 2021 [6,7]. There is increasing evidence that people with multiple sclerosis (pwMS) treated with high-efficacy disease-modifying drugs (DMD), those targeting B cells, have an impaired humoral response to vaccination with mRNA vaccines [8,9,10]. This observation is of concern, as pwMS are at increased risk for acquiring infections. The Swiss MS Society recommended, in August 2021, administration of a third vaccine dose in MS patients treated with B cell-targeted disease-modifying therapies and an insufficient humoral immune response after two vaccine doses [21]

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