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. 2022 Aug 1:13:920865.
doi: 10.3389/fimmu.2022.920865. eCollection 2022.

Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases

Yen-Ju Chen  1   2   3   4 , Po-Liang Cheng  3   5 , Wen-Nan Huang  1   4   6 , Hsin-Hua Chen  1   4   6   7   8   9 , Hong-Wei Chen  3 , Jun-Peng Chen  3 , Ching-Tsai Lin  1 , Kuo-Tung Tang  1   8 , Wei-Ting Hung  1   6   10 , Tsu-Yi Hsieh  1   10 , Yi-Hsing Chen  1   4 , Yi-Ming Chen  1   3   4   6   8 , Tzu-Hung Hsiao  3   11   12
Affiliations

Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases

Yen-Ju Chen et al. Front Immunol. .

Abstract

Objectives: To 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).

Methods: From 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.

Results: The 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.

Conclusions: mRNA-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.

Keywords: COVID-19 vaccine; anti-rheumatic medications; autoimmune; rheumatic disease; single-cell RNA sequencing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Comparison of the anti-SARS-CoV-2 IgG level after (A) the first dose of COVID-19 vaccines and (B) the second dose of COVID-19 vaccines among healthy controls and patients with individual rheumatic diseases; and (C) comparison of the percentage of seropositivity rate of RA patients using csDMARDs, TNF inhibitors, non-TNF bDMARDs, and JAK inhibitors after the first and second doses of COVID-19 vaccines. SLE, systemic lupus erythematosus; RA, rheumatoid arthritis; csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; TNF, tumor necrosis factor; bDMARDs, biologic disease-modifying antirheumatic drugs; JAK, Janus kinase. **p < 0.001.
Figure 2
Figure 2
The comprehensive cell atlas of peripheral blood mononuclear cells of rheumatoid arthritis patients with high and low anti-SARS-CoV2-IgG antibodies. (A) UMAP visualization of peripheral blood mononuclear cells from rheumatoid arthritis patients. (B) The proportion of cell types between high and low anti-SARS-CoV2-IgG antibody groups. (C) Volcano plot of CD16-monocyte showed differential expressed genes of high anti-SARS-CoV2-IgG antibody group comparing to low anti-SARS-CoV2-IgG antibody group. (D) Pathway analysis between high and low anti-SARS-CoV2-IgG antibody groups.
Figure 3
Figure 3
Comparisons of (A) cell atlas of peripheral blood mononuclear cells, (B) the proportions of cell types from each participant and (C) healthy controls from GSE201534 vs. patients with rheumatoid arthritis from our study. Pathway analysis of CD16+ and CD16-monocyte between (D) high anti-SARS-CoV2-IgG antibody group and (E) low anti-SARS-CoV2-IgG antibody group from our study vs. healthy control from GSE201534. .
Figure 4
Figure 4
Differential crosstalks between high and low anti-SARS-CoV2-IgG antibody groups among each cell populations in rheumatoid arthritis patients. (A) Circle plot shows the MHC class II pathway outgoing and incoming signaling among high anti-SARS-CoV2-IgG antibody group (left) and low anti-SARS-CoV2-IgG antibody group (right); (B) Bubble plot shows the selected ligand-receptor interactions between NK cells, monocytes and pDC.
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