Temporal evolution of humoral and T-cell specific immune response to COVID-19 mRNA vaccine in multiple sclerosis

ABSTRACT

Background: Although a full course of vaccine against Sars- Cov-2 is effective in most patients with MS (PwMS), the duration of the protection and the efficacy of a booster dose remain poorly explored, especially across different disease modifying treatments (DMTs). Aim(s) To characterize humoral and T-cell immune response along time and following third dose of COVID-19 vaccination in PwMS. Method(s) From an established cohort evaluated at baseline (T0), PwMS were recruited after 24 weeks (T1) from the first cycle of mRNA vaccine and 4 weeks after third dose (T2). At each timepoint we evaluated the serological response by measuring the anti- Region-Binding-Domain (RBD). Cell-mediated response was analyzed by computing interferon (IFN)-gamma in response to spike peptides. Result(s) The baseline cohort consisted of 134 PwMS [mean age 46.6+/-10.8 years;F92;mean disease duration 15.1+/-9.4 years;26.9% ocrelizumab (OCR) 30.6% fingolimod (FTY), 16.4% cladribine (CLA), 26.1%IFN-s-1a (IFNB)]. Of them, 109 were reassessed at T1, 78 at T2 and 64 completed all evaluations. In the whole cohort there was a significant reduction (p<0.0001) in anti- RBD rate from T0 [76% positive, median 52.8 BAU/ml Interquartile Range (IQR) 1150.9] to T1 (57.8% positive, median 13.2 BAU/ml IQR 95.98] and a significant 20- and 5-fold increase in median titer at T2 (75% positive, median 272.3 BAU/ml IQR 4212.3) from T1 and T0 respectively (p<0.0001). Median IFN-gamma level at T2 was significantly higher than those evaluated at T1 (p<0.0001) and T0 (p=0.009). These latter results were consistent across all DMTs. At T1 the highest detectable anti-RBD response was found in CLA (100%, median 87.7 BAU/ml IQR 22) and IFNB (93.5%;median 126.3 BAU/ml IQR 149.2) cohort, while PwMS treated with FTY and OCR showed 60% (median 8.25 BAU/ml IQR 34.3) and 21% (median 0.8 BAU/ml IQR 6) rate of anti-RBD response respectively. At T2 100% PwMS showed positive anti-RBD response except those treated with OCR (23.8% positive, median 0.6 BAU/ml IQR 4.1). IFN-gamma-S-specific T-cell response was reduced in FTY cohort at both T1 and T2 (3.3 % positive, median 0.8 pg/ml IQR 3.1 and 0.6 pg/ml IQR 2.4 respectively). Conclusion(s) A third dose of COVID-19 vaccine reinforces both humoral and cell-mediated immune response in PwMS on DMTs. Despite vaccination, PwMS treated with OCR and FTY show lower humoral and T-cell specific immune response respectively, suggesting the need of specific treatment to halt COVID-19 in case of infection.