Humoral response to SARS-CoV-2-mRNA vaccine in multiple sclerosis patients treated with high efficacy disease-modifying therapies

ABSTRACT

Introduction: Since the worldwide launch of the SARS-CoV-2 vaccine campaign, there have been many uncertainties regarding the immune response to vaccination in patients with multiple sclerosis (pwMS), particularly those on high efficacy disease-modifying therapies (DMTs). Aim: To evaluate humoral response to NT162b2-mRNACovid- 19 vaccine in pwMS on high efficacy DMTs compared to healthy controls (HCs). Methods: We collected serum samples before the first dose and 7 days after the second dose of the NT162b2-mRNA-Covid-19 vaccine from 54 HCs and 93 pwMS on high efficacy DMTs (Ocrelizumab/OCR, Fingolimod/FNG, Natalizumab/NTZ). Exclusion criteria history of Covid-19, baseline positive SARSCoV- 2 IgG antibodies, steroids administration within the month prior to the first dose of vaccine. Sera were tested using the LIAISONRSARS-CoV-2 TrimericSIgG assay for the detection of IgG antibodies to SARS-CoV-2 spike protein. The IgG-titers were expressed in Binding Antibody Units (BAU) with 33.8 BAU/mL as cut-off. Results: Sera of 51 HCs and 80pwMS (31 OCR, 25 FNG, 24 NTZ) were analyzed, while 3 HCs and 13 pwMS (4OCR, 5FNG, 4NTZ) were kept out due to exclusion criteria. Age, sex, and disease duration were similar across groups. Seven days after the second dose of the vaccine, SARS-CoV-2 IgG antibodies were detected in all HCs and pwMS on NTZ, in 17(54.8%) pwMS on OCR and 10(40%) pwMS on FNG. pwMS on OCR (median 59.8 BAU/mL;P25-75 4.81-598) and FNG (median 21.5;P25-75 7.49-116) showed a significant blunted response (p<0.0001, both) when compared with HCs (median 1860;P25-75 1180-4865) and NTZ patients (p<0.0001, both). pwMS on NTZ mounted a humoral response (median 3015;P25-75 1495-4905) similar to HCs (p=0.52). Interestingly, we observed a positive association between humoral response and time elapsed since the last OCR infusion (rho 0.46,p=0.001) and an inverse correlation between humoral response and treatment duration in pwMS on FTY (rho -0.57,p=0.004). No correlation was found with CD20 levels in the OCR group. Discussion: We found a clear blunted humoral response to NT162b2-mRNA-Covid-19 vaccine in pwMS treated with OCR and FNG, with a significant relationship with treatment duration in FNG-treated pwMS and time elapsed since the last infusion in the OCR-treated pwMS. Contrariwise, we found an efficient humoral response in NTZ-treated pwMS. Further data are needed to inform which strategy could optimize the response to vaccines in pwMS on OCR and FTY.