Longitudinal study of humoral and cellular responses to COVID-19 mRNA vaccines with and without 3rd (booster) dose in MS patients on ocrelizumab: 24-week results from VIOLA (NCT04843774)

ABSTRACT

Background: Patients on OCR have attenuated antibody, but largely intact T-cell responses to COVID-19 vaccination. Little is known about durability of post-vaccine responses in OCR-treated patients. Objective(s) To examine antibody and cellular responses to mRNA COVID-19 vaccines (Pfizer, BioNTech/Moderna) in Ocrelizumab (OCR)-treated MS patients over 24-week period. Method(s) MS patients on OCR were recruited from NYU (New York City) and Rocky Mountain at CU (Denver) MS Centers. Antibody responses to SARS-CoV-2 spike proteins were assessed with multiplex bead-based (MBI) immunoassays, and cellular responses to SARS-CoV-2 Spike protein with ELISpot and activation induced marker (AIM) panel in a Cytek Aurora full-spectrum flow cytometry platform. Data on samples collected pre-vaccine and 4-, 12-, 24-weeks post 2-doses and 4-, 12-weeks post-third dose will be presented. Result(s) 40/61 enrollees (age 38.3+/-10.9;77.5% female;57.5% non-white) had 24-week post-vaccination data and 9 patients had 4-week post 3rd dose data. Antibody response increased from prevaccine level of 972.0 U/mL to 6307.4 U/mL at week-4 (p=0.0002), then decreased to 4633.8 u/mL at week-12 (26% decrease from week-4, p=0.1377), and further to 2878.4 u/mL at week-24 (37% decrease from week-12, p value=0.109). Spikespecific IFNgamma T-cell responses by ELIspot were 125.7 SFU/106 cells pre-vaccine, increased to 362.9 SFU/106 cells at week-4 (p=0.009), then to 511.5 SFU/106 cells at week-12 (40.9% increase relative to 4-week time-point, p=0.8474), and remained elevated at 501.7 SFU/106 cells at week-24 (p=0.7393, 1.9% compared to week 12). 4-week post 3rd dose, Ab level increased to 5094.8 U/mL (189.9% compared to pre-3rd dose, p =0.076) and IFNgamma responses to 1253.3 SFU/106 cells (484.5% increase, p=0.037). Conclusion(s) Antibody responses to 2-series vaccine peaked at 4 weeks and trended downward thereafter, while cellular responses were sustained at 24 weeks. Third-dose resulted in marked increases in both antibody and T-cell responses 4-weeks. Expanded analyses, including in-depth immunophenotyping and 12-week post 3rd vaccination responses will be presented.