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

• Published in: Frontiers in immunology 2023-08, Vol.14, p.1091237-1091237
• Main Authors: Zhao, Meie, Wang, Chunxia, Li, Peiqiang, Sun, Tao, Wang, Jing, Zhang, Shasha, Ma, Qinglong, Ma, Fengdie, Shi, Wenjing, Shi, Maoning, Ma, Yapeng, Pan, Yunyan, Zhang, Hui, Xie, Xiaodong
• Format: Article
• Language: English
• Subjects: hepatitis B vaccine; high immune response; Immunology; no immune response; peripheral blood mononuclear cell; single-cell RNA sequencing
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1091237

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 high CD16 low KLRG1 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 high CD16 low KLRG1 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.