Three to four mRNA COVID-19 vaccine in multiple sclerosis patients on immunosuppressive drugs: seroconversion and variants neutralization.

Abstract

An enhanced SARS-CoV-2 vaccine regimen could improve humoral vaccine response in patients with multiple sclerosis (MS) treated by anti-CD20. We aimed to evaluate the serological response and the neutralizing activity after BNT162b2 primary and booster vaccination in MS patients, including patients on anti-CD20 receiving a primary vaccine regimen enhanced with 3 injections. In this prospective longitudinal cohort study of 90 patients (47 on anti-CD20, 10 on fingolimod, 33 on natalizumab, dimethylfumarate or teriflunomide), anti-SARS-CoV-2 receptor binding domain (RBD) IgG antibodies were quantified and their neutralization capacity was evaluated by ELISA (GenScript) and a virus neutralization test against B.1 historical strain, delta and omicron variants, before and after 3 to 4 BNT162b2 injections. After primary vaccination scheme, anti-RBD positivity rate was strongly decreased in patients on anti-CD20 (28%[15%;44%] after 2 shots, 45%[29%;62%] after 3 shots) and fingolimod (50%[16%;84%]) compared to other treatments (100%[90%;100%]). Neutralization activity was also decreased in patients on anti-CD20 and fingolimod, and notably low for Omicron variant in all patients (0-22%). Delayed booster vaccination was performed in 54 patients, leading to a mild increase of anti-RBD seropositivity in patients on anti-CD20, although still lower compared to other treatments (65%[43%;84%] versus 100%[87%;100%] respectively). After booster, Omicron neutralization activity remained low on anti-CD20 and fingolimod treated patients, but strongly increased in patients on other treatments (91%[72%;99%]). In MS patients on anti-CD20, an enhanced primary vaccination scheme moderately increased anti-RBD seropositivity and anti-RBD antibody titer, but neutralization activity remained modest even after a 4th booster injection.