Humoral immune response to SARS-CoV-2 third vaccination in patients with multiple sclerosis and healthy controls: A prospective multicenter study

Krajnc, Nik; Hegen, Harald; Traxler, Gerhard; Leutmezer, Fritz; Pauli, Franziska Di; Kornek, Barbara; Zulehner, Gudrun; Riedl, Katharina; Dürauer, Sophie; Bauer, Angelika; Kratzwald, Sarah; Klotz, Sigrid; Winklehner, Michael; Deisenhammer, Florian; Guger, Michael; Höftberger, Romana; Berger, Thomas; Bsteh, Gabriel

doi:10.1016/j.msard.2022.104009

Cited by 7 publications

(5 citation statements)

References 19 publications

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“…This is despite the fact that cladribine seems to affect lymphocyte counts until two years after last dose [20] . Current findings are in line with previous studies on the subject by Brill et al (n = 34) [11] , Tortorella et al (n = 20) [17] , Milo et al (n = 35) [16] , Grothe et al (n = 38) [12] , Kranjc et al (n = 26) [14] and Achiron et al (n = 48) [4] , where all cladribine treated patients reached seropositivity. In the study by Maglione et al (n = 7) [15] , 1 patient did not seroconvert after the first vaccination cycle.…”

Section: Discussionsupporting

confidence: 92%

“…Consequently, data on the humoral response to SARS-CoV-2 infection in cladribine treated MS patients is limited. Several studies report successful humoral responses to both infection and vaccination, with nearly all cladribine treated patients reaching seropositivity after vaccination (cumulative sample size of 208 patients) [4] , [11] , [12] , [13] , [14] , [15] , [16] , [17] . Regarding vaccination, most workgroups advised vaccination at least 4 weeks before next dose and a minimum interval varying between 12 and 18 weeks after the last dose, depending on the country [18] , [19] .…”

Section: Introductionmentioning

confidence: 99%

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Humoral immune response after SARS-CoV-2 vaccination in cladribine-treated multiple sclerosis patients

Mimpen,

Kreiter,

Kempkens

et al. 2024

Vaccine: X

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Humoral immune response after SARS-CoV-2 vaccination in cladribine-treated multiple sclerosis patients

Mimpen,

Kreiter,

Kempkens

et al. 2024

Vaccine: X

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“…Moreover, there should have been a preformed memory formation of both B and T cells during first and second vaccination, presumably having been modulated by initial DMTs, forming the basis for the immune response following booster vaccination. Since booster vaccination leads to an enhanced humoral immune response even in B cell depleted patients, while complete B cell depletion is associated with decreased probability of seroconversion (OR 0.14; p = 0.021) ( 16 ), it might be possible that the humoral immune response measured here under ofatumumab treatment might have been due to third vaccination and not the levels achieved following second vaccination. This, however, is not supported by the data since robust longitudinal data are missing.…”

Section: Discussionmentioning

confidence: 96%

Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination

Faissner

Heitmann²,

Plaza-Sirvent³

et al. 2022

Front. Immunol.

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ObjectiveThe pandemic induced by SARS-CoV-2 has huge implications for patients with immunosuppression that is caused by disorders or specific treatments. Especially approaches targeting B cells via anti-CD20 therapy are associated with impaired humoral immune response but sustained cellular immunity. Ofatumumab is a human anti-CD20 directed antibody applied in low dosages subcutaneously, recently licensed for Multiple Sclerosis (MS). Effects of early ofatumumab treatment on alterations of immune cell composition and immune response towards SARS-CoV-2 are incompletely understood.MethodsWe here investigated immune cell alterations in early ofatumumab (Ofa) treated patients and effects on humoral (titer, neutralization capacity against wild type, Delta and Omicron) and cellular immune responses in Ofa treated MS patients following a third vaccination against SARS-CoV-2 compared to healthy controls.ResultsWe show that a mean treatment duration of three months in the Ofa group led to near complete B cell depletion in line with altered composition of certain CD4+ T cell subpopulations such as enhanced frequencies of naive and a decrease of non-suppressive regulatory T cells (Tregs). Titer and neutralization capacity against SARS-CoV-2 variants was impaired while cellular immune response was sustained, characterized by a strong T helper 1 profile (Th1).InterpretationIn summary, low dosage ofatumumab treatment elicits sustained depletion of B cells in line with alterations of immune cells, mainly Tregs. This is associated with impaired humoral immune response towards SARS-CoV-2 vaccination but preserved, Th1 driven cellular immunity adding crucial information regarding early effects of low dosage anti-CD20 therapy on humoral and cellular immunity.

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“…Previous studies have mainly evaluated humoral response ( 1 – 4 ) or cytokine production after SARS-CoV-2 vaccination ( 5 – 8 ) and few focused on dissection of both the B and T cell compartments of the cellular immune response ( 9 , 10 ). Some have studied the effects of only a specific treatment, such as anti-CD20 antibody drugs ( 11 , 12 ), or only a specific time after vaccination ( 13 – 18 ).…”

Section: Introductionmentioning

confidence: 99%

Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination

Orrù,

Serra,

Marongiu

et al. 2024

Front. Immunol.

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IntroductionDisease-modifying therapies (DMTs) have been shown to improve disease outcomes in multiple sclerosis (MS) patients. They may also impair the immune response to vaccines, including the SARS-CoV-2 vaccine. However, available data on both the intrinsic immune effects of DMTs and their influence on cellular response to the SARS-CoV-2 vaccine are still incomplete.MethodsHere, we evaluated the immune cell effects of 3 DMTs on the response to mRNA SARS-CoV-2 vaccination by comparing MS patients treated with one specific therapy (fingolimod, dimethyl fumarate, or natalizumab) with both healthy controls and untreated patients. We profiled 23 B-cell traits, 57 T-cell traits, and 10 cytokines, both at basal level and after stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS patients, treated with DMTs or untreated, and 32 healthy controls. Measurements were made before vaccination and at three time points after immunization.Results and DiscussionMS patients treated with fingolimod showed the strongest immune cell dysregulation characterized by a reduction in all measured lymphocyte cell classes; the patients also had increased immune cell activation at baseline, accompanied by reduced specific immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike specific B cells progressively increased over the three time points after vaccination, even when antibodies measured from the same samples instead showed a decline. Our findings demonstrate that repeated booster vaccinations in MS patients are crucial to overcoming the immune cell impairment caused by DMTs and achieving an immune response to the SARS-CoV-2 vaccine comparable to that of healthy controls.

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Humoral immune response to SARS-CoV-2 third vaccination in patients with multiple sclerosis and healthy controls: A prospective multicenter study

Cited by 7 publications

References 19 publications

Humoral immune response after SARS-CoV-2 vaccination in cladribine-treated multiple sclerosis patients

Humoral immune response after SARS-CoV-2 vaccination in cladribine-treated multiple sclerosis patients

Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination

Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination

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