AUTHOR=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 

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1091237

DOI=10.3389/fimmu.2023.1091237

ISSN=1664-3224

ABSTRACT=<p>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<sup>high</sup>CD16<sup>low</sup>KLRG1<sup>high</sup> 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 <italic>HLA-B</italic>, <italic>HLA-DRB5</italic>, <italic>BLNK</italic>, <italic>BLK</italic>, <italic>IL4R</italic>, <italic>SCIMP</italic>, <italic>JUN</italic>, <italic>CEBPB</italic>, <italic>NDFIP1</italic>, and <italic>TXNIP</italic>—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 <italic>GNLY</italic>, <italic>NKG7</italic>, <italic>GZMB</italic>, <italic>GZMM</italic>, <italic>KLRC1</italic>, <italic>KLRD1</italic>, <italic>PRF1</italic>, <italic>CST7</italic>, and <italic>CTSW</italic>, was significantly higher in CD3<sup>high</sup>CD16<sup>low</sup>KLRG1<sup>high</sup> 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.</p>