156. The immunological response to COVID-19 vaccination in patients with ANCA-associated vasculitis treated with rituximab

Background: Landmark clinical trials have demonstrated efficacy of SARS-CoV-2 vaccination in preventing severe COVID-19, however most participants in these trials were healthy volunteers. In particular, vaccine performance in immunosuppressed individuals, such as those with ANCA-associated vasculitis (AAV) is unknown. Rituximab (RTX) has become an important treatment for AAV, however this B cell depleting agent has previously evidenced impaired humoral response following influenza vaccines and now there are similar concerns regarding reduced immunogenicity to SARS-CoV-2 vaccines. In this study, we aimed to characterise the immune response of the ChAdOx1 (Astra Zeneca) vaccine in RTX treated AAV patients. (1) Methods: The OCTAVE trial was a UK based, multi-centre, multi-disease prospective cohort study designed to assess the immune response to SARS-CoV-2 vaccination in immunosuppressed individuals, including patients with AAV treated with RTX within the prior 12 months. Peripheral blood samples were taken for quantitative IgG response to SARS-CoV-2 spike antigen (anti-S) and IFN T cell responses to SARS-CoV-2 antigens at baseline (where possible), immediately prior to second SARS-CoV-2 vaccine dose and 28 days post-second dose. Results were compared to a group of healthy controls from the UK PITCH (Protective Immunity from T cells in Healthcare workers) study. Results: Of 455 cases recruited for full immune response analysis, 29 had AAV and 93 were healthy controls. Baseline demographics were described (Table 1). At 4 weeks post-second SARS-CoV-2 vaccine dose 27.6% (8/29) AAV patients demonstrated anti-S seroconversion, compared to 100% (93/93) healthy controls. Further, 89.7% of AAV patients had an anti-S antibody response that was less that the lowest titre achieved in the healthy control group. When compared to other OCTAVE disease cohorts, AAV patients had the lowest serological conversion rate and lowest median anti-S titre. The median SARS-CoV-2 specific T cell response in the AAV group was 98 (IQR: 40-178) IFN secreting T cells / 106 peripheral blood mononuclear cells (PBMC), while the equivalent result in the healthy control group was 60 (IQR: 20-136) (Table 1). Conclusions: Early analysis indicates that individuals with AAV have a substantially blunted antibody response to SARS-CoV-2 compared to a healthy population, but a comparable T-cell response. This may suggest that AAV patients have some degree of protection from SARS-CoV-2 vaccination, but clinical evaluation of this population is awaited. Analyses of additional immunological parameters, such as neutralising antibody responses and broader immunoglobulin analysis, are ongoing. Disclosures: None relevant to this study. Table 1: Demographics and anti-Spike seroconversion at 4 weeks in healthy controls and AAV patients Healthy controls AAV N (whole cohort) 231 30 Age; N (%) 18 – 40 186 (81%) 10 (33%) 50 – 64 37 (16%) 12 (40%) 65 + 7 (3%) 8 (27%) Missing data 1 (0%) 0 (0%) Sex; N (%) Female (%) 156 (68%) 16 (53%) N (full immune response at 4 weeks) 93 29 Anti-S seroconversion; N (%) 93 (100%) 8 (27.6%) Anti-S titre; U/ml [Median(IQR)] 11,514 (3,324-23,302) 0.4 (0.4-24.5) IFN secreting T cells; per 106 PBMC [Median(IQR)] 60 (20-136). 98 (40-178