Immune response to the third COVID-19 vaccine dose is related to lymphocyte count in multiple sclerosis patients treated with fingolimod

Anat Achiron, Mathilda Mandel, Michael Gurevich, Sapir Dreyer-Alster, David Magalashvili, Polina Sonis, Mark Dolev, Shay Menascu, Gil Harari, Shlomo Flechter, Rina Falb

Research output: Contribution to journalArticlepeer-review


Background: The majority of multiple sclerosis [MS] patients treated with fingolimod fail to develop a protective level of IgG humoral and adaptive cellular immune responses following full BNT162b2 SARS-CoV-2 vaccination. Objective: To compare the efficacy of the third COVID-19 vaccine dose in vaccine non-responders fingolimod-treated MS patients. Study design: This is a prospective 3-month, single-center, randomized clinical trial. Methods: Twenty relapsing MS patients who had been on fingolimod therapy ≥ 12 months and failed to develop humoral IgG immune response to 2-dose Pfizer BNT162b2 COVID-19 vaccination were randomized into two groups: fingolimod-continuation group and fingolimod-discontinuation group. Humoral and memory cellular immune responses were assessed within 1 and 3 months following the third Pfizer BNT162b2 vaccine dose and compared between the groups. Results: A higher rate of patients in the fingolimod-discontinuation group [n = 8/10] compared to fingolimod-continuation group [n = 2/10] developed positive SARS-COV-2 IgG. Median IgG titer 1 month following the third dose was 202.3 BAU/ml vs. 26.4 BAU/ml, respectively, p = 0.022. The development of IgG humoral response correlated with absolute lymphocyte count. Specific SARS-COV-2 memory B cell and T cell immune responses were not detected in both groups, either at 1 month or 3 months following the third COVID-19 vaccine dose. Conclusions: Short period of fingolimod treatment discontinuation was associated with the development of humoral protection but not with adaptive cellular immunity.

Original languageEnglish
Pages (from-to)2286-2292
Number of pages7
JournalJournal of Neurology
Issue number5
StatePublished - May 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.


  • Cellular immunity
  • COVID-19
  • Fingolimod
  • Humoral immunity
  • IgG antibody
  • Multiple sclerosis
  • Third BNT162b2 SARS-CoV-2 vaccine dose

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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