Neutralizing Antibody Response to SARS-CoV-2 Vaccination in Multiple Sclerosis

ABSTRACT

Objective: To investigate the humoral immune response following SARS-CoV-2 vaccination in patients with multiple sclerosis (pwMS) and to determine the effect of disease modifying therapies (DMT) on the vaccination response. Background: Coronavirus disease 19 (COVD-19), a highly transmissible and potentially fatal illness caused by SARS-CoV-2, emerged as a global pandemic in early 2020. Several vaccines, including 2 innovative mRNA vaccines, were developed against this virus. To reduce relapse rates and slow disability accumulation, pwMS are often treated with DMTs which have anti-inflammatory properties and regulate adaptive immunity. An important clinical issue concerns the impact of DMTs on the efficacy of SARS-CoV-2 vaccination, and the eventual need for booster doses. In this study, we measured the titers of anti-SARS-CoV-2 neutralizing antibodies (nAbs) in pwMS following SARS-CoV-2 vaccination. Design/Methods: We conducted a prospective longitudinal study in pwMS at the Ohio State University (OSU) MS Center. Longitudinal serum samples were obtained from pwMS prior to and after the administration of the SARS-CoV-2 vaccine. These samples were analyzed for nAbs against SARS-CoV-2 spike protein using a novel pseudotyped-lentivirus-based virus neutralization assay. OSU health care workers (HCWs) served as healthy controls. Results: Of eighty-three consented subjects, fifty-two had post vaccination serum samples analyzed. Although pwMS did not exhibit drastically different nAb titers compared to HCWs, 21% (n=11) did not have detectable nAb titers post-vaccination (NT50 < 40)-including 9 patients on B-cell depleting therapies, 1 on sphingosine 1-phosphate modulator, and 1 on no DMT. Compared to patients not on DMT, pwMS on B-cell depleting therapies exhibited 7-fold lower nAb titers, while those on fumarates or beta-interferon exhibited no significant difference to patients not on DMT. Conclusions: Humoral immune response to the SARS-CoV-2 vaccine may be attenuated by certain DMTs, most notably B-cell depleting drugs. Further studies are underway to determine the effect of booster vaccine on nAb levels.