Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases
ObjectivesTo investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.920865/full |
| _version_ | 1818014980863164416 |
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| author | Yen-Ju Chen Yen-Ju Chen Yen-Ju Chen Yen-Ju Chen Po-Liang Cheng Po-Liang Cheng Wen-Nan Huang Wen-Nan Huang Wen-Nan Huang Hsin-Hua Chen Hsin-Hua Chen Hsin-Hua Chen Hsin-Hua Chen Hsin-Hua Chen Hsin-Hua Chen Hong-Wei Chen Jun-Peng Chen Ching-Tsai Lin Kuo-Tung Tang Kuo-Tung Tang Wei-Ting Hung Wei-Ting Hung Wei-Ting Hung Tsu-Yi Hsieh Tsu-Yi Hsieh Yi-Hsing Chen Yi-Hsing Chen Yi-Ming Chen Yi-Ming Chen Yi-Ming Chen Yi-Ming Chen Yi-Ming Chen Tzu-Hung Hsiao Tzu-Hung Hsiao Tzu-Hung Hsiao |
| author_facet | Yen-Ju Chen Yen-Ju Chen Yen-Ju Chen Yen-Ju Chen Po-Liang Cheng Po-Liang Cheng Wen-Nan Huang Wen-Nan Huang Wen-Nan Huang Hsin-Hua Chen Hsin-Hua Chen Hsin-Hua Chen Hsin-Hua Chen Hsin-Hua Chen Hsin-Hua Chen Hong-Wei Chen Jun-Peng Chen Ching-Tsai Lin Kuo-Tung Tang Kuo-Tung Tang Wei-Ting Hung Wei-Ting Hung Wei-Ting Hung Tsu-Yi Hsieh Tsu-Yi Hsieh Yi-Hsing Chen Yi-Hsing Chen Yi-Ming Chen Yi-Ming Chen Yi-Ming Chen Yi-Ming Chen Yi-Ming Chen Tzu-Hung Hsiao Tzu-Hung Hsiao Tzu-Hung Hsiao |
| author_sort | Yen-Ju Chen |
| collection | DOAJ |
| description | ObjectivesTo investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq).MethodsFrom September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis.ResultsThe anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (β: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase 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 antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group.ConclusionsmRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. 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. |
| first_indexed | 2024-04-14T06:52:07Z |
| format | Article |
| id | doaj.art-172f2a227eed43fdb1724a247df38c60 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T06:52:07Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-172f2a227eed43fdb1724a247df38c602022-12-22T02:07:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.920865920865Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseasesYen-Ju Chen0Yen-Ju Chen1Yen-Ju Chen2Yen-Ju Chen3Po-Liang Cheng4Po-Liang Cheng5Wen-Nan Huang6Wen-Nan Huang7Wen-Nan Huang8Hsin-Hua Chen9Hsin-Hua Chen10Hsin-Hua Chen11Hsin-Hua Chen12Hsin-Hua Chen13Hsin-Hua Chen14Hong-Wei Chen15Jun-Peng Chen16Ching-Tsai Lin17Kuo-Tung Tang18Kuo-Tung Tang19Wei-Ting Hung20Wei-Ting Hung21Wei-Ting Hung22Tsu-Yi Hsieh23Tsu-Yi Hsieh24Yi-Hsing Chen25Yi-Hsing Chen26Yi-Ming Chen27Yi-Ming Chen28Yi-Ming Chen29Yi-Ming Chen30Yi-Ming Chen31Tzu-Hung Hsiao32Tzu-Hung Hsiao33Tzu-Hung Hsiao34Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, TaiwanInstitute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, TaiwanDepartment of Medical Research, Taichung Veterans General Hospital, Taichung, TaiwanSchool of Medicine, National Yang-Ming Chiao Tung University, Taipei, TaiwanDepartment of Medical Research, Taichung Veterans General Hospital, Taichung, TaiwanDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDivision of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, TaiwanSchool of Medicine, National Yang-Ming Chiao Tung University, Taipei, TaiwanDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, TaiwanDivision of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, TaiwanSchool of Medicine, National Yang-Ming Chiao Tung University, Taipei, TaiwanDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, TaiwanDepartment of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, TaiwanInstitute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, TaiwanInstitute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, TaiwanDepartment of Medical Research, Taichung Veterans General Hospital, Taichung, TaiwanDepartment of Medical Research, Taichung Veterans General Hospital, Taichung, TaiwanDivision of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, TaiwanDivision of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, TaiwanInstitute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, TaiwanDivision of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, TaiwanDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan0Department of Medical Education, Taichung Veterans General Hospital, Taichung, TaiwanDivision of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan0Department of Medical Education, Taichung Veterans General Hospital, Taichung, TaiwanDivision of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, TaiwanSchool of Medicine, National Yang-Ming Chiao Tung University, Taipei, TaiwanDivision of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, TaiwanDepartment of Medical Research, Taichung Veterans General Hospital, Taichung, TaiwanSchool of Medicine, National Yang-Ming Chiao Tung University, Taipei, TaiwanDepartment of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, TaiwanInstitute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, TaiwanDepartment of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan1Department of Public Health, Fu Jen Catholic University, New Taipei City, Taiwan2Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, TaiwanObjectivesTo investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq).MethodsFrom September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis.ResultsThe anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (β: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase 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 antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group.ConclusionsmRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.920865/fullCOVID-19 vaccinerheumatic diseaseautoimmuneanti-rheumatic medicationssingle-cell RNA sequencing |
| spellingShingle | Yen-Ju Chen Yen-Ju Chen Yen-Ju Chen Yen-Ju Chen Po-Liang Cheng Po-Liang Cheng Wen-Nan Huang Wen-Nan Huang Wen-Nan Huang Hsin-Hua Chen Hsin-Hua Chen Hsin-Hua Chen Hsin-Hua Chen Hsin-Hua Chen Hsin-Hua Chen Hong-Wei Chen Jun-Peng Chen Ching-Tsai Lin Kuo-Tung Tang Kuo-Tung Tang Wei-Ting Hung Wei-Ting Hung Wei-Ting Hung Tsu-Yi Hsieh Tsu-Yi Hsieh Yi-Hsing Chen Yi-Hsing Chen Yi-Ming Chen Yi-Ming Chen Yi-Ming Chen Yi-Ming Chen Yi-Ming Chen Tzu-Hung Hsiao Tzu-Hung Hsiao Tzu-Hung Hsiao Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases Frontiers in Immunology COVID-19 vaccine rheumatic disease autoimmune anti-rheumatic medications single-cell RNA sequencing |
| title | Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases |
| title_full | Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases |
| title_fullStr | Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases |
| title_full_unstemmed | Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases |
| title_short | Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases |
| title_sort | single cell rna sequencing to decipher the immunogenicity of chadox1 ncov 19 azd1222 and mrna 1273 vaccines in patients with autoimmune rheumatic diseases |
| topic | COVID-19 vaccine rheumatic disease autoimmune anti-rheumatic medications single-cell RNA sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.920865/full |
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