MSCOVID Fingolimod inhibits T and B cell response

M

Opinion is just that opinion and you can take it or leave it, but I do report things with a slant on how it fits with what we have said or done. This is what part of public engaugement is about….bringing your research to the public eye.

The problem is can we say anything negative?……..I guess the answer is no:-(.

I know what you think…In the words of Villanelle

One may say it depends on how things are put. Should we accept things without comment?

For example. Should we make comment on things said such as an introductory pre-amble which you know is a preamble, such as “there is limited data on how disease-modifying therapies (DMTs) alter SARS-CoV-2 mRNA vaccine immunogenicity in patients with autoimmune diseases”…..A quick search of COVID and VACCINATION and MULTIPLE SCLEROSIS throws up 329 hits on pubmed, COVID and VACCINATION throws up 38,501 hits and a search on COVID and VACCINATION and FINGOLIMOD throws up 50 hits (Not all will be relevent). So is this limited data?…I’ll let you decide. B

Does this new study show anything new?…sure it does….does it tell us something we didn’t know already?

I am aware that responses are inhibited with anti-CD20 and fingolimod and notably a reduced T and B cell response with fingolimod. I would argue that this study re-inforces a view made some time ago as replication is a key part of the scientific process.

SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod.

Meyer-Arndt L, Braun J, Fauchere F, Vanshylla K, Loyal L, Henze L, Kruse B, Dingeldey M, Jürchott K, Mangold M, Maraj A, Braginets A, Böttcher C, Nitsche A, de la Rosa K, Ratswohl C, Sawitzki B, Holenya P, Reimer U, Sander LE, Klein F, Paul F, Bellmann-Strobl J, Thiel A, Giesecke-Thiel C.J Neurol Neurosurg Psychiatry. 2022 Jul 14:jnnp-2022-329395.

Background: SARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there are limited data on how disease-modifying therapies (DMTs) alter SARS-CoV-2 mRNA vaccine immunogenicity in patients with autoimmune diseases.

Methods: As part of a prospective cohort study, we investigated the induction, stability and boosting of vaccine-specific antibodies, B cells and T cells in patients with multiple sclerosis (MS) on different DMTs after homologous primary, secondary and booster SARS-CoV-2 mRNA vaccinations. Of 126 patients with MS analysed, 105 received either anti-CD20-based B cell depletion (aCD20-BCD), fingolimod, interferon-β, dimethyl fumarate, glatiramer acetate, teriflunomide or natalizumab, and 21 were untreated MS patients for comparison.

Results: In contrast to all other MS patients, and even after booster, most aCD20-BCD- and fingolimod-treated patients showed no to markedly reduced anti-S1 IgG, serum neutralising activity and a lack of receptor binding domain-specific and S2-specific B cells. Patients receiving fingolimod additionally lacked spike-reactive CD4+ T cell responses. The duration of fingolimod treatment, rather than peripheral blood B and T cell counts prior to vaccination, determined whether a humoral immune response was elicited.

Conclusions: The lack of immunogenicity under long-term fingolimod treatment demonstrates that functional immune responses require not only immune cells themselves, but also access of these cells to the site of inoculation and their unimpeded movement. The absence of humoral and T cell responses suggests that fingolimod-treated patients with MS are at risk for severe SARS-CoV-2 infections despite booster vaccinations, which is highly relevant for clinical decision-making and adapted protective measures, particularly considering additional recently approved sphingosine-1-phosphate receptor antagonists for MS treatment.

So why talk about this paper? Does it say can we or how we mitigate the problem?

This is background for stuff to come for the lab

COI: Multiple

Disclaimer: These views are the opinion of the author and no-one else.

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MouseDoctor

2 comments

  • Should patients on Fingolimod even bother getting the vaccine (third dose, or boosters)? I got the first two doses of Moderna, but never went in for the third dose or boosters, after getting Covid, and then seeing some of the studies come out about effectiveness, I was wondering if it was even worth it. It feels like the answer is no, but some will say, even if it doesn’t work, there’s no harm in getting it… just in case???

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