Abstract
Background
COVID-19 vaccination-induced Spike antibodies are attenuated in people living with multiple sclerosis (pwMS) on high-efficacy disease-modifying therapies (DMTs). It is currently unknown whether vaccine boosters will elicit a greater protective antibody cross-reactivity against emerging variants of concern, such as XBB.1 and BQ.1.1.
Objective
We aimed to determine the breadth of Spike antibody immunoreactivity in pwMS after COVID-19 vaccination.
Methods Spike antibodies to Wuhan, XBB.1, and BQ1.1 SARS-CoV-2 were assessed in paired sera from pwMS (1-month post-second and -third doses, n=37) and general community controls (n=10). Demographic and treatment information was available in all patients.
Results
At 1-month post-third dose, pwMS who did not seroconvert (n=12) were treated with ocrelizumab (11/21) and fingolimod (1/3). Natalizumab, fingolimod, ocrelizumab, dimethyl fumarate, and ofatumumab were associated with decreased titers of Spike antibody compared to controls, whereas alemtuzumab, cladribine, and IFNs were associated to titers comparable to controls. When serial Wuhan Spike antibody titers were compared at 1-month post-second and -third doses, most DMTs (alemtuzumab, fingolimod, cladribine, dimethyl fumarate, interferon-beta, natalizumab, ocrelizumab, and ofatumumab) were able to increase or maintain their Spike antibody titers. Spike antibody titers against XBB.1 and BQ1.1 was reduced by 80% compared to the Wuhan titers in all groups. The third dose increased median titres compared to the second dose in most DMTs including the CD20-depleting DMTs but to a much lesser extent (ocrelizumab n=10; ofatumumab n=2).
Conclusion
Some SARS-CoV-2 variants and some DMTs reduce Spike antibody titres or prevent seroconversion even after a third dose of vaccine.