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The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination

BACKGROUND: Sphingosine-one phosphate receptor (S1PR) modulation inhibits S1PR1-mediated lymphocyte migration, lesion formation and positively-impacts on active multiple sclerosis (MS). These S1PR modulatory drugs have different: European Union use restrictions, pharmacokinetics, metabolic profiles...

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Autores principales: Baker, David, Forte, Eugenia, Pryce, Gareth, Kang, Angray S., James, Louisa K., Giovannoni, Gavin, Schmierer, Klaus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). Published by Elsevier B.V. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9678390/
https://www.ncbi.nlm.nih.gov/pubmed/36470168
http://dx.doi.org/10.1016/j.msard.2022.104425
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author Baker, David
Forte, Eugenia
Pryce, Gareth
Kang, Angray S.
James, Louisa K.
Giovannoni, Gavin
Schmierer, Klaus
author_facet Baker, David
Forte, Eugenia
Pryce, Gareth
Kang, Angray S.
James, Louisa K.
Giovannoni, Gavin
Schmierer, Klaus
author_sort Baker, David
collection PubMed
description BACKGROUND: Sphingosine-one phosphate receptor (S1PR) modulation inhibits S1PR1-mediated lymphocyte migration, lesion formation and positively-impacts on active multiple sclerosis (MS). These S1PR modulatory drugs have different: European Union use restrictions, pharmacokinetics, metabolic profiles and S1PR receptor affinities that may impact MS-management. Importantly, these confer useful properties in dealing with COVID-19, anti-viral drug responses and generating SARS-CoV-2 vaccine responses. OBJECTIVE: To examine the biology and emerging data that potentially underpins immunity to the SARS-CoV-2 virus following natural infection and vaccination and determine how this impinges on the use of current sphingosine-one-phosphate modulators used in the treatment of MS. METHODS: A literature review was performed, and data on infection, vaccination responses; S1PR distribution and functional activity was extracted from regulatory and academic information within the public domain. OBSERVATIONS: Most COVID-19 related information relates to the use of fingolimod. This indicates that continuous S1PR1, S1PR3, S1PR4 and S1PR5 modulation is not associated with a worse prognosis following SARS-CoV-2 infection. Whilst fingolimod use is associated with blunted seroconversion and reduced peripheral T-cell vaccine responses, it appears that people on siponimod, ozanimod and ponesimod exhibit stronger vaccine-responses, which could be related notably to a limited impact on S1PR4 activity. Whilst it is thought that S1PR3 controls B cell function in addition to actions by S1PR1 and S1PR2, this may be species-related effect in rodents that is not yet substantiated in humans, as seen with bradycardia issues. Blunted antibody responses can be related to actions on B and T-cell subsets, germinal centre function and innate-immune biology. Although S1P1R-related functions are seeming central to control of MS and the generation of a fully functional vaccination response; the relative lack of influence on S1PR4-mediated actions on dendritic cells may increase the rate of vaccine-induced seroconversion with the newer generation of S1PR modulators and improve the risk-benefit balance IMPLICATIONS: Although fingolimod is a useful asset in controlling MS, recently-approved S1PR modulators may have beneficial biology related to pharmacokinetics, metabolism and more-restricted targeting that make it easier to generate infection-control and effective anti-viral responses to SARS-COV-2 and other pathogens. Further studies are warranted.
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spelling pubmed-96783902022-11-22 The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination Baker, David Forte, Eugenia Pryce, Gareth Kang, Angray S. James, Louisa K. Giovannoni, Gavin Schmierer, Klaus Mult Scler Relat Disord Review Article BACKGROUND: Sphingosine-one phosphate receptor (S1PR) modulation inhibits S1PR1-mediated lymphocyte migration, lesion formation and positively-impacts on active multiple sclerosis (MS). These S1PR modulatory drugs have different: European Union use restrictions, pharmacokinetics, metabolic profiles and S1PR receptor affinities that may impact MS-management. Importantly, these confer useful properties in dealing with COVID-19, anti-viral drug responses and generating SARS-CoV-2 vaccine responses. OBJECTIVE: To examine the biology and emerging data that potentially underpins immunity to the SARS-CoV-2 virus following natural infection and vaccination and determine how this impinges on the use of current sphingosine-one-phosphate modulators used in the treatment of MS. METHODS: A literature review was performed, and data on infection, vaccination responses; S1PR distribution and functional activity was extracted from regulatory and academic information within the public domain. OBSERVATIONS: Most COVID-19 related information relates to the use of fingolimod. This indicates that continuous S1PR1, S1PR3, S1PR4 and S1PR5 modulation is not associated with a worse prognosis following SARS-CoV-2 infection. Whilst fingolimod use is associated with blunted seroconversion and reduced peripheral T-cell vaccine responses, it appears that people on siponimod, ozanimod and ponesimod exhibit stronger vaccine-responses, which could be related notably to a limited impact on S1PR4 activity. Whilst it is thought that S1PR3 controls B cell function in addition to actions by S1PR1 and S1PR2, this may be species-related effect in rodents that is not yet substantiated in humans, as seen with bradycardia issues. Blunted antibody responses can be related to actions on B and T-cell subsets, germinal centre function and innate-immune biology. Although S1P1R-related functions are seeming central to control of MS and the generation of a fully functional vaccination response; the relative lack of influence on S1PR4-mediated actions on dendritic cells may increase the rate of vaccine-induced seroconversion with the newer generation of S1PR modulators and improve the risk-benefit balance IMPLICATIONS: Although fingolimod is a useful asset in controlling MS, recently-approved S1PR modulators may have beneficial biology related to pharmacokinetics, metabolism and more-restricted targeting that make it easier to generate infection-control and effective anti-viral responses to SARS-COV-2 and other pathogens. Further studies are warranted. The Author(s). Published by Elsevier B.V. 2023-01 2022-11-22 /pmc/articles/PMC9678390/ /pubmed/36470168 http://dx.doi.org/10.1016/j.msard.2022.104425 Text en © 2022 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Review Article
Baker, David
Forte, Eugenia
Pryce, Gareth
Kang, Angray S.
James, Louisa K.
Giovannoni, Gavin
Schmierer, Klaus
The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination
title The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination
title_full The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination
title_fullStr The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination
title_full_unstemmed The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination
title_short The impact of sphingosine-1-phosphate receptor modulators on COVID-19 and SARS-CoV-2 vaccination
title_sort impact of sphingosine-1-phosphate receptor modulators on covid-19 and sars-cov-2 vaccination
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9678390/
https://www.ncbi.nlm.nih.gov/pubmed/36470168
http://dx.doi.org/10.1016/j.msard.2022.104425
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