Single-cell RNA sequencing reveals the transcriptomic characteristics of peripheral blood mononuclear cells in hepatitis B vaccine non-responders

Meie Zhao; Chunxia Wang; Peiqiang Li; Tao Sun; Jing Wang; Shasha Zhang; Qinglong Ma; Fengdie Ma; Wenjing Shi; Maoning Shi; Yapeng Ma; Yunyan Pan; Hui Zhang; Xiaodong Xie

doi:10.3389/fimmu.2023.1091237

Single-cell RNA sequencing reveals the transcriptomic characteristics of peripheral blood mononuclear cells in hepatitis B vaccine non-responders

Front Immunol. 2023 Aug 1:14:1091237. doi: 10.3389/fimmu.2023.1091237. eCollection 2023.

Authors

Meie Zhao^{1

2}, Chunxia Wang², Peiqiang Li¹, Tao Sun³, Jing Wang¹, Shasha Zhang¹, Qinglong Ma¹, Fengdie Ma¹, Wenjing Shi¹, Maoning Shi¹, Yapeng Ma⁴, Yunyan Pan⁵, Hui Zhang⁶, Xiaodong Xie¹

Affiliations

¹ School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.
² Department of Laboratory Medicine, The First People's Hospital of Lanzhou, Lanzhou, Gansu, China.
³ Clinical Laboratory, Huzhou Central Hospital, Huzhou Hospital Affiliated with Zhejiang University, Huzhou, Zhejiang, China.
⁴ Department of Laboratory Medicine, The First People's Hospital of Tianshui, Tian Shui, Gansu, China.
⁵ Department of Laboratory Medicine, The Second Hospital of Lanzhou University, Lanzhou, Gansu, China.
⁶ Virus Laboratory, Gansu Provincial Center for Disease Control and Prevention, Lanzhou, Gansu, China.

Abstract

The emergence of a vaccine against hepatitis B has proven to be an important milestone in the prevention of this disease; however, 5%-10% of vaccinated individuals do not generate an immune response to the vaccine, and its molecular mechanism has not been clarified. In this study, single-cell RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from three volunteers with a high immune response (HR) and three with no immune response (NR) to the hepatitis B vaccine. We found that the antigen-presenting activity scores of various antigen-presenting cells, the mitogen-activated protein kinase (MAPK) pathway activity scores of naive B cells, and the cell activity scores of three types of effector T cells were significantly decreased, whereas the cytotoxicity scores of CD3^highCD16^lowKLRG1^high natural killer T (NKT) cells were significantly increased in the NR group compared with those in the HR group. Additionally, the expression levels of some classical molecules associated with distinct signaling pathways-including HLA-B, HLA-DRB5, BLNK, BLK, IL4R, SCIMP, JUN, CEBPB, NDFIP1, and TXNIP-were significantly reduced in corresponding subsets of PBMCs from the NR group relative to those of the HR group. Furthermore, the expression of several cytotoxicity-related effector molecules, such as GNLY, NKG7, GZMB, GZMM, KLRC1, KLRD1, PRF1, CST7, and CTSW, was significantly higher in CD3^highCD16^lowKLRG1^high NKT cells derived from non-responders. Our study provides a molecular basis for the lack of response to the hepatitis B vaccine, including defective antigen presentation, decreased T cell activity, and reduced IL-4 secretion, as well as novel insight into the role of NKT cells in the immune response to the hepatitis B vaccine.

Keywords: hepatitis B vaccine; high immune response; no immune response; peripheral blood mononuclear cell; single-cell RNA sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Gene Expression Profiling
Hepatitis B Vaccines*
Humans
Leukocytes, Mononuclear
Sequence Analysis, RNA
Transcriptome*

Substances

Hepatitis B Vaccines

Grants and funding

This study was funded by the Gansu Province Science and Technology Innovation Service Platform Construction Project (18JR2TA024) and the Youth Science and Technology Foundation of Gansu Province (20JR5RA141).