S1849 ARMOR Study: Immunogenicity and Safety of Recombinant Spike Protein Vaccine in Patients With Inflammatory Bowel Disease and Liver Transplant Recipients Comparable to Healthy Controls

Introduction: mRNA coronavirus disease 2019 (COVID-19) vaccines are safe in immunosuppressed populations, data on protein-based vaccines remain limited. We evaluated the immunogenicity and safety of Novavax COVID-19 vaccine (NVX-CoV2601) in immunosuppressed patients. Methods: This single-center, prospective ARMOR study included adults with inflammatory bowel disease (IBD) or solid organ transplant recipients receiving immunosuppressive therapy with ≥3 prior COVID-19 vaccine doses. Participants received one NVX-CoV2601 booster with follow-up at one and 6 months. Antibody concentrations were measured using anti-spike IgG ELISA and pseudovirus neutralization. The primary outcome was change in antibody concentration from baseline to one month post-vaccination in ARMOR participants. Secondary outcomes included evaluating sustained antibody concentration at 6 months post-immunization, humoral immunogenicity in the ARMOR cohort compared to an age/sex-matched healthy control cohort, adverse events, and safety (IBD flares or transplant rejection). Statistical analyses included paired t-tests for antibody concentration changes and ANCOVA with baseline adjustment for between-group comparisons. GMTs and 95% confidence intervals (CIs) were calculated using log-transformed values. Results: Twenty-one patients, 18 IBD and 3 liver transplant recipients, were enrolled in ARMOR and compared with 42 age/sex-matched healthy controls (Mean age 47.65, 60% males). In the ARMOR cohort, anti-spike IgG GMT increased significantly post-immunization (22,969 to 66,639 EU/mL at one month; 2.9-fold increase, P = 0.001). Healthy controls showed an increase from 54,812 to 129,813 EU/mL (2.4-fold increase; P < 0.001). Neutralizing antibody analysis showed similar trends, with ARMOR participants demonstrating a 3.6-fold increase from baseline (GMT 174.6 ID50 to 628.0 ID50; P = 0.002) vs controls' 1.6-fold increase (P = 0.001), with no statistically significant difference between groups at day 28 after baseline adjustment (GMTR 1.12; P = 0.728). At 6 months, both binding and neutralizing antibodies waned faster in immunosuppressed subjects (GMTR 0.60, P = 0.009 for binding; GMTR 0.44, P = 0.008 for neutralizing) compared to controls. NVX-CoV2601 was well tolerated, with mild reactogenicity, and was not associated with IBD flares or solid organ rejection. Conclusion: NVX-CoV2601 was safe and immunogenic with similar antibody responses in immunosuppressed patients compared to healthy controls, in contrast to that seen with mRNA vaccines.