Background: Few studies investigated the immune response to SARS-CoV-2 vaccine in patients with multiple sclerosis (pwMS) treated with natalizumab (NTZ) and found a short-term efficient humoral response; however, there are no studies assessing the levels of SARS-CoV-2 IgG antibodies in pwMS treated with NTZ over time. Methods: Humoral immune response to BNT162b2 mRNA COVID-19 vaccine was assessed in a group of 26 pwMS on NTZ up to 6 months after a full COVID-19 vaccination cycle and compared it with 43 age- and sex-matched group of HC. Serum samples were collected before the first dose (T0), and 4 weeks (T1) and 6 months (T2) after the first dose of BNT162b2 mRNA COVID-19 vaccine. The LIAISON® SARS-CoV-2 TrimericS-IgG assay (DiaSorin-S.p.A.) was employed for the detection of IgG antibodies to SARS-CoV-2 spike protein (cutoff for positive IgG antibodies: 33.8 BAU/mL). Results: At T1 and T2, both groups showed an efficient humoral response to BNT162b2 mRNA COVID-19 vaccine. A significant reduction of IgG antibodies to SARS-CoV-2 spike protein was detected at T2 both in pwMS and in HC, but SARS-CoV-2 IgG antibodies were still above the cutoff limit in all participants. Conclusions: pwMS on NTZ develop and maintain a long-term humoral response after a full COVID-19 vaccination cycle comparable to their healthy peers, and these findings are relevant for clinicians called to counsel about COVID-19 mRNA vaccine timing and booster doses in pwMS treated with NTZ.
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