SARS-CoV-2 mRNA Vaccination in People with Multiple Sclerosis Treated with Fingolimod: Protective Humoral Immune Responses May Develop after the Preferred Third Shot.

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

doi:10.3390/vaccines10020341

Lutz Achtnichts, Johann Sellner + Show 6 more

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https://doi.org/10.3390/vaccines10020341

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Abstract

Evidence suggests limited development of protective IgG responses to mRNA-based vaccines in sphingosine-1-phosphate receptor (S1PR)-modulator treated individuals with multiple sclerosis (MS). We studied the extent of the humoral immune response after the preferred third mRNA SARS-CoV-2 vaccine in S1PR-modulator treated people with MS (pwMS) and insufficient IgG responses after the standard immunization scheme. Eight pwMS that were treated with fingolimod received a third homologous SARS-CoV-2 mRNA vaccine dose, either the Moderna’s mRNA-1273 or Pfizer-BioNTech’s BNT162b2 vaccine. We quantified the serum levels of IgG antibodies against the receptor-binding domain of SARS-CoV-2 four weeks later. An antibody titer of 100 AU/mL or more was considered protective. After the third vaccination, we found clinically relevant IgG titers in four out of eight individuals (50%). We conclude that the humoral immune response may reach protective levels after the third preferred dose of the homologous SARS-CoV-2 mRNA vaccine. Vaccine shots in S1PR-modulator treated pwMS ahead of schedule may be a strategy to overcome insufficient humoral immune responses following the standard vaccination scheme.

Highlights

Coronaviruses are a diverse group of viruses capable of infecting various animal species, and they can cause mild to severe respiratory infections in humans
We identified 29 people with MS (pwMS) treated with the sphingosine-1-phosphate receptor (S1PR)-modulator fingolimod (FTY, Novartis, Basel, Switzerland) who were examined for seroconversion after the standard two shots of the BNT162b2 or mRNA-1273 vaccines
As part of an ongoing project to determine the risk of less effective vaccination in patients treated with immunomodulatory drugs in this monocentric evaluation, we studied the IgG response against the spike protein after a second and third shot of an mRNAbased vaccine against SARS-CoV-2 in pwMS receiving the S1PR-modulator FTY

Summary

Introduction

Coronaviruses are a diverse group of viruses capable of infecting various animal species, and they can cause mild to severe respiratory infections in humans. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease, termed “coronavirus infectious disease 2019” (COVID-19). This multi-organ disease poses an ongoing global threat to economics and public health [1]. Several reports corroborated that vaccination on treatment with S1PR modulators are associated with reduced seroconversion rates and attenuated responses [17–19]. This observation was extended to mRNA vaccines against SARS-CoV-2 [20–24]

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