Background: COVID-19 is a potentially fatal respiratory illness, caused by the novel coronavirus, SARS-CoV-2, which developed into the ongoing pandemic claiming the lives of over 575,000 people in the United States and over 3 million worldwide as of April 2021. Antibodies against the spike glycoprotein are believed to confer immunity to SARS-CoV-2. Some disease modifying therapy (DMTs) used to treat multiple sclerosis (MS) impair responses to vaccines. Objectives: This study is designed to evaluate and compare the effect of DMTs on antibody response to mRNA vaccines for prevention of COVID-19. Methods: This prospective open-label observational study is recruiting 120 participants (natalizumab [NTZ] n=30, ocrelizumab [OCR] n=30, fumarate [FUM] (dimethyl fumarate [DMF] or diroximel fumarate [DRF] n=30), and interferon [IFN, any IFN and peginterferon beta-1a] n=30) ages 18 65 years inclusive, with a diagnosis of relapsing MS who are stable on their current DMT for >6 months. Participants will have serum collected to quantitatively analyze anti-spike SARS-CoV-2 IgG levels (sCOVg, Siemens Healthineers) at baseline and then 8 weeks, 24 weeks, 48 weeks, and 72 weeks after 1st dose of mRNA-1273 COVID-19 vaccine (Moderna). IFNs will be used as the reference to compare Geometric Mean Titers (GMT) of anti-spike SARS-CoV-2 IgG levels between groups. Summary statistics will be used for demographic and safety data. Results: Currently 31 patients are enrolled (NTZ, n=11; OCR, n=6; FUM, n=10; and IFN, n=4); 87% are female. 55% of patients have received both doses of vaccine. Mean (SD) age was 48 (10) years old for the patients enrolled (NTZ, 47 ; OCR, 49 ; FUM, 47 ; and IFN, 54 ). The mean duration on MS therapy was 5.2 (5) years for NTZ, 2.5 (0.8) years for OCR, 3.9 (3.1) years for FUM, and 8.3 (5.6) years for IFN. GMT quantitative analysis for anti-spike SARS-CoV-2 IgG results at 8 weeks from initial vaccine dose will be presented. Conclusions: This study will provide healthcare practitioners with additional quantitative data on the humoral immune response to mRNA-1273 COVID-19 vaccination in MS patients treated by various DMTs.