Weighted gene co-expression network-based identification of genetic effect of mRNA vaccination and previous infection on SARS-CoV-2 infection

Yue He; Mengzi Sun; Yan Xu; Chengxiang Hu; Yanfang Wang; Yuan Zhang; Jiaxin Fang; Lina Jin

doi:10.1016/j.cellimm.2023.104689

Weighted gene co-expression network-based identification of genetic effect of mRNA vaccination and previous infection on SARS-CoV-2 infection

Cell Immunol. 2023 Mar:385:104689. doi: 10.1016/j.cellimm.2023.104689. Epub 2023 Feb 10.

Authors

Yue He¹, Mengzi Sun², Yan Xu³, Chengxiang Hu⁴, Yanfang Wang⁵, Yuan Zhang⁶, Jiaxin Fang⁷, Lina Jin⁸

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun, Jilin 130021, China. Electronic address: heyue21@mails.jlu.edu.cn.
² Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun, Jilin 130021, China. Electronic address: smz20@mails.jlu.edu.cn.
³ Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun, Jilin 130021, China. Electronic address: yanxu21@mails.jlu.edu.cn.
⁴ Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun, Jilin 130021, China. Electronic address: hucx22@mails.jlu.edu.cn.
⁵ Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun, Jilin 130021, China. Electronic address: yanfang21@mails.jlu.edu.cn.
⁶ Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun, Jilin 130021, China. Electronic address: yuanzhang21@mails.jlu.edu.cn.
⁷ Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun, Jilin 130021, China. Electronic address: fangjx21@mails.jlu.edu.cn.
⁸ Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, No.1163 Xinmin Street, Changchun, Jilin 130021, China. Electronic address: jinln@jlu.edu.cn.

Abstract

To investigate the effect conferred by vaccination and previous infection against SARS-CoV-2 infection in molecular level, weighted gene co-expression network analysis was applied to screen vaccination, prior infection and Omicron infection-related gene modules in 46 Omicron outpatients and 8 controls, and CIBERSORT algorithm was used to infer the proportions of 22 subsets of immune cells. 15 modules were identified, where the brown module showed positive correlations with Omicron infection (r = 0.35, P = 0.01) and vaccination (r = 0.62, P = 1 × 10^-6). Enrichment analysis revealed that LILRB2 was the unique gene shared by both phosphatase binding and MHC class I protein binding. Pathways including "B cell receptor signaling pathway" and "FcγR-mediated phagocytosis" were enriched in the vaccinated samples of the highly correlated LILRB2. LILRB2 was also identified as the second hub gene through PPI network, after LCP2. In conclusion, attenuated LILRB2 transcription in PBMC might highlight a novel target in overcoming immune evasion and improving vaccination strategies.

Keywords: BNT162b2 mRNA vaccine; COVID-19; LILRB2; MHC class I protein binding; SARS-CoV-2 Omicron infection; WGCNA.

MeSH terms

COVID-19* / genetics
COVID-19* / prevention & control
Gene Regulatory Networks
Humans
Leukocytes, Mononuclear
SARS-CoV-2
Vaccination
mRNA Vaccines* / immunology

Substances

mRNA Vaccines

Supplementary concepts

SARS-CoV-2 variants