This study aims at understanding the impact of ofatumumab treatment on the development of cellular and humoral immune responses to initial and booster SARS-CoV-2 mRNA vaccines.

Recently developed SARS-CoV-2 mRNA vaccines have been shown to efficiently protect healthy individuals against COVID-19 and contribute greatly towards fighting the COVID-19 pandemic. However, only limited data is available about vaccine-induced immune responses to SARS-CoV-2 mRNA vaccines in immunosuppressed patients.

KYRIOS is an ongoing two-cohort, multicenter, open-label, prospective clinical study designed to characterize immune responses to SARS-CoV-2 mRNA vaccines in patients with relapsing MS treated or to be treated with ofatumumab. Patients received their initial or booster SARS-CoV-2 mRNA vaccination either prior (cohort 1) or during ofatumumab treatment (cohort 2). SARS-CoV-2-specific T-cell responses as well as serum total and neutralizing antibodies were measured one week and one month after the second dose of the initial vaccination or after booster vaccination. 

Interim analysis will show the effect of ofatumumab treatment on the immune response after booster vaccination. Almost all patients (22/23) who received their initial vaccination before the study showed an increase in neutralizing antibody titer after their first booster. Antibody titers were comparable in patients boostered during continuous ofatumumab treatment (n=15) and the control group (n=8). 3/4 seroconverted after receiving their booster vaccine during stable ofatumumab treatment. Increase of neutralizing antibody titers after booster was also observed in patients who received their initial vaccination while stable on ofatumumab suggesting the successful development of immune memory cells during continuous ofatumumab treatment. Data from the trial will also be compared to findings from other SARS-CoV-2 vaccination studies in MS patients.

KYRIOS data show that SARS-CoV-2 booster vaccines increase the immune response in the vast majority of ofatumumab patients independently of their treatment status during initial vaccination and emphasize the importance of booster vaccination in these patients.