ABSTRACT
Objective To assess adaptive immunity to SARS-CoV-2 in anti-CD20 treated individuals with mRNA vaccination. Background Anti-CD20 therapies attenuate humoral responses to vaccines. However, their effect on T cell responses is less clear. We examined B and T cell responses following COVID-19 vaccination in patients receiving anti-CD20 therapy for multiple sclerosis (MS) and other autoimmune inflammatory neurologic diseases (AINDs, e.g., autoimmune encephalitis, stiff person syndrome, etc.). Design/Methods MS and AIND patients on anti-CD20 therapies were prospectively enrolled for longitudinal analysis of antibody and T cell responses after a 3rd COVID-19 vaccination. Serum antibodies against the receptorbinding domain of the S1 spike protein (RBD-S1 IgG), neutralizing antibodies, and SARS-CoV-2 CD8 T cell responses, using activationinduced markers (AIM) and INF-gamma release assays (EUROIMMUN, Germany), were measured at various time points including prevaccination, post initial vaccination series, and 4 and 12 weeks after 3rd dose. Results Thirty-four MS and AIND participants are enrolled. Results for these patients (mean age 52 years-old, 79% female, 21 Pfizer, 13 Moderna) demonstrated attenuated RBD IgG antibody responses. However, a robust CD8 T cell response was observed, following a two-dose series, compared to non-immunosuppressed, age-matched vaccinated controls or unvaccinated with severe SARS-CoV-2 infection (p = 0.01). T cell response was sustained long-term (>12 weeks post 3rd dose) in all 11 anti-CD20 patients analyzed thus far. Collections are completed for all participants at 12 weeks and analysis to be completed by 05/15/22. Further analysis includes correlation of the INF- gamma release assay compared to RBD-CD8 T cell response detected by AIM assay. Conclusions Results suggest that patients treated with anti-CD20 therapy generate a robust CD8 T cell response to SARS-CoV-2 mRNA after three doses but remain with attenuated humoral immune responses. Our observational study will provide important data to guide vaccine management in patients on or anticipating anti-CD20 therapy.
ABSTRACT
Objective: To assess adaptive immunity to SARS-CoV-2 in anti-CD20 treated individuals with mRNA vaccination as it relates to spike binding IgG, neutralizing antibody titers, and T cell response. Background: Anti-CD20 therapies attenuate humoral responses to vaccines. Their effect on T cell responses is unclear. We examined B and T cell responses with COVID-19 vaccination in patients receiving anti-CD20 therapy for multiple sclerosis (MS) and other autoimmune inflammatory neurologic diseases (AINDs). Design/Methods: Patients on anti-CD20 therapies were prospectively enrolled for longitudinal analysis of antibody and T cell responses before and after COVID-19 vaccination. Serum antibodies against the receptor-binding domain of the S1 spike protein (RBD-S1 IgG), neutralizing antibodies, and SARS-CoV-2 CD4 and CD8 T cell levels responses using activation-induced markers and INF-gamma release assay were measured at various time points including pre-vaccination, less than 12 weeks and greater than 12 weeks post initial vaccination series, and 4 and 12 weeks after 3rd “booster” vaccination. Results: Twenty-five MS and AIND participants are enrolled as of 10/11/21 with projected enrollment complete by December 2021 (50-60 total). Preliminary results for 17 of these patients (mean age 44 years-old, 83% female, 16 Pfizer, 1 Moderna) demonstrated attenuated RBD IgG antibody responses. However, CD8 T cell response is robust compared to non-immunosuppressed, age-matched controls (n=22) less than 12 weeks after two dose series (p value = 0.0069) and sustained long-term (>12 weeks) in all eight anti-CD20 patients tested thus far. Additional analysis will include comparison between pre and post 3rd vaccination at 4- and 12-week timepoints. Conclusions: Early results suggest that patients treated with anti-CD20 therapy generate a robust CD8 T cell response to SARS-CoV-2 mRNA post initial series of vaccination but remain with attenuated humoral immune responses. Our observational study will provide important data to guide vaccine management in patients on or anticipating anti-CD20 therapy.