POS1249 EFFICACY AND SAFETY OF ChAdOx1 nCoV-19/AZD1222 AND mRNA-1273 VACCINES: A COMPARATIVE STUDY IN PATIENTS WITH AUTOIMMUNE RHEUMATIC DISEASES

BackgroundSeveral studies have demonstrated immunogenicity after COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD) [1], but the differences between mRNA-based and vector vaccines and the cellular responses to COVID-19 vaccines according to distinct immunogenicity in AIRD patients are still unclear.ObjectivesTo investigate the differences in efficacy and safety between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with AIRD, and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) by single-cell RNA sequencing (scRNA-seq).MethodsFrom September 16 to November 15, 2021, we consecutively enrolled 243 participants aged ≥20 years with AIRD who received COVID-19 vaccination, of whom 113 were immunized with AZD1222 and 130 with mRNA-1273. The level of serum IgG antibodies to the SARS-CoV-2 receptor-binding domain on the spike protein S1 subunit was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells were isolated from two RA patient with high anti-SARS-CoV-2 IgG level and four RA patients with low level for scRNA-seq and cell-cell communication signal was analyzed by CellChat.ResultsThe anti-SARS-CoV-2 IgG seropositivity rate was 78.8% (89/113) for AZD1222 and 83.1% (108/130) for mRNA-1273. The level of anti-SARS-CoV-2 IgG was higher in patients who received mRNA-1273 than in those who received AZD1222 (β: 30.15, 95% CI: 11.67-48.63, p=0.002) (Table 1). Prednisolone-equivalent dose >5 mg/day and methotrexate (MTX) use in AIRD patients, and non-anti-tumor necrosis factor (TNF)-α biologics and Janus kinase (JAK) inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibody level, and enriched pathways related to antigen presentation via major histocompatibility complex class II (MHC class II) were found (Figure 1). HLA-DRA and CD4 interaction was vigorous among all identified MHC-II pathway and was enhanced in high anti-SARS-CoV2-IgG antibody group.Table 1.Multivariate analysis of anti-SARS-CoV-2 IgG level in patients with rheumatic diseases following COVID-19 vaccinesMultivariate analysisβ95% CIp valueMedicationsGlucocorticoidsNot usedReference≤5 mg/day−22.48(−56.33,11.37)0.192>5 mg/day−23.45(−43.54,-3.36)0.022Methotrexate−24.89(−45.70,-4.08)0.019Targeted therapiesTargeted therapies group Not usedReference TNF inhibitor−15.78(−41.33,9.76)0.224 Non-TNF bDMARD−25.27(−55.47,4.93)0.100 JAK inhibitor−17.08(−47.23,13.07)0.265VaccineChAdOx1 nCoV-19/AZD1222ReferencemRNA-127330.15(11.67,48.63)0.002TNF: tumor necrosis factor, bDMARDs: biologic disease-modifying antirheumatic drugs, JAK: Janus kinase.Figure 1.The comprehensive cell atlas of PBMC of RA patients with high and low anti-SARS-CoV2-IgG antibodies. A) UMAP visualization of PBMC cells from RA patients. B) The proportion of cell types between high and low antibody groups. C) Volcano plot of CD16-monocyte showed differential expressed genes. D) Pathway analysis between high and low antibody groups; PRBC: peripheral blood mononuclear cell, RA: rheumatoid arthritis, NK cell: natural killer cell, pDC: plasmacytoid dendritic cell, CLP: common lymphoid progenitor.ConclusionmRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in patients with AIRD. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.References[1]Geisen UM, Berner DK, Tran F, et al. Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort. Ann Rheum Dis. 2021;80:1306-1311.AcknowledgementsThe authors thank the Biostatistics Task Force of Taichung Veterans General Hospital for their assistance with the statistical analysis in this study.Disclosure of InterestsNone declared