Humoral efficacy of the third SARS-CoV-2 vaccine dose in Multiple Sclerosis subjects undergoing different disease-modifying therapies

Background: It remains unclear how vaccine doses and combinations of vaccination and infection affect the magnitude and quality of immune responses, particularly against novel SARS-CoV-2 variants in subjects with immune-related disorders, such as people with multiple sclerosis (pwMS). Several studies have evaluated the duration of anti-SARS-CoV-2 immune protection in healthy individuals; however clinical data suggest an attenuated short-term humoral response to SARS-CoV-2 vaccines in pwMS receiving disease-modifying therapies (DMTs). Methods: In this prospective study, we evaluated the humoral response to the third (3rd) BNT162b2 vaccine (booster) dose in a monocentric cohort of pwMS undergoing eight different DMTs, all without previous SARS-CoV-2 infection. Quantitative determination of SARS-CoV-2 IgG Spike titre was carried out by anti-SARS-CoV-2 S assay in 65 pwMS and 9 healthy controls, all without previous SARS-CoV-2 infection. Moreover, these measurements were also compared to their relative levels at 21 days (T1) and similar to 6 months (T2) after the second (2nd) vaccination. Results: We observed that the humoral response to the booster dose in Interferon beta-1a-, Dimethyl fumarate-and Teriflunomide-treated pwMS is comparable to healthy controls, while increased in Cladribine-treated pwMS. Additionally, the 3rd dose elicits a seroconversion in the 100% of pwMS under Fingolimod and in the 65% of those under Ocrelizumab. Moreover, multivariate regression analysis showed that treatment with Interferon beta-1a, Dimethyl fumarate and Cladribine positively associates with an increased humoral response.Conclusions: Taken together this evidence strongly indicates the importance of the booster dose to enhance SARS-CoV-2-specific immunity especially in immunocompromised subjects, such as pwMS under DMTs.