158. Altered Antibody Response to SARS-CoV-2 Vaccination in Patients with Immune-mediated Disease on Immunosuppressive Therapy

Background: The development of highly effective SARS-CoV-2 vaccines has provided the opportunity to combat the global COVID-19 pandemic. Vaccine trials that supported their authorization largely excluded individuals receiving immunosuppressive medications. While a growing number of studies have demonstrated impaired antibody production to SARS-CoV-2 vaccines among immunosuppressed patients, our understanding of the risk factors for suboptimal immune response remains incomplete. Following authorization of SARS-CoV-2 vaccines, we leveraged existing registries and multi-specialty clinics to collect longitudinal pre- and post-vaccine (prime-dose and booster) bio-samples. Methods: We enrolled patients with immune-mediated disease who were currently on immunosuppressive therapy. Reactivity to the SARS-CoV-2 spike protein receptor binding domain (RBD) and N-terminal domain (NTD) were assessed by ELISAs using recombinant proteins produced in-house. Neutralizing antibodies were measured using a surrogate virus neutralization assay to determine the percent inhibition of RBD binding to ACE-2 (cPass, GenScript). Results: To date, we have enrolled 80 patients (65% female, 81% white, age range 13 to 85; 56% vasculitis, 14% glomerular disease, 30% other) and 12 healthy controls not on immunosuppressive therapy. Sera from 64 patients collected 30 to 90 days after the prime vaccine series (41% Moderna, 59% Pfizer) has been tested (Table 1). Over half (34/64, 53%) developed neutralizing antibodies, all of whom had reactivity to RBD and NTD, including 4 patients who had received rituximab therapy within 3 months of their first vaccine dose. Thirty patients (47%) failed to develop neutralizing antibodies. Of these, 40% (12/30) showed reactivity to RBD and NTD. All healthy controls developed robust neutralizing antibodies and reactivity to RBD and NTD. Conclusions: These data indicate that the antibody response following SARS-CoV-2 vaccination is altered in patients with immune-mediated disease. A substantial proportion of immunosuppressed patients developed reactive, but not neutralizing, antibodies to viral epitopes. Elucidating factors that contribute to sufficient humoral and cellular immunization is critical for the development of effective vaccination strategies for this vulnerable population. Disclosures: None Table 1. SARS-CoV-2 reactivity by medication type in patients with immune-mediated diseases Medication type N (%) RBD+ NTD+ Neut Ab+ Rituximab 30 (47%) 18 (60%) 18 (60%) 12 (40%) AZA 4 (6%) 4 (100%) 4 (100%) 4 (100%) MMF 15 (23%) 10 (67%) 11 (73%) 6 (40%) Methotrexate 4 (6%) 4 (100%) 4 (100%) 4 (100%) Other 11 (17%) 10 (91%) 8 (73%) 8 (73%) Total 64 46 (72%) 45 (70%) 34 (53%) Abbreviations: MMF – mycophenolate mofetil, AZA – azathioprine. “Other” includes tumor necrosis factor alpha inhibitor, janus kinase inhibitor, Plaquenil, prednisone, and Tacrolimus