Circulating Tfh cell and subsets distribution are associated with low\u2010responsiveness to hepatitis B vaccination

Mingjuan Yin,Gang Liu,Dongmei Liang,Hao Tang,Tingyu Lian,Jinmei Zeng,Yongzhen Xiong,Qian Hong,Jingxiao Huang,Jindong Ni

doi:10.1186/s10020-021-00290-7

Abstract

BackgroundAn estimated 5–10 % of healthy vaccinees lack adequate antibody response following receipt of a standard three-dose hepatitis B vaccination regimen. The cellular mechanisms responsible for poor immunological responses to hepatitis B vaccine have not been fully elucidated to date.MethodsThere were 61 low responders and 56 hyper responders involved in our study. Peripheral blood samples were mainly collected at D7, D14 and D28 after revaccinated with a further dose of 20 µg of recombinant hepatitis B vaccine.ResultsWe found low responders to the hepatitis B vaccine presented lower frequencies of circulating follicular helper T (cTfh) cells, plasmablasts and a profound skewing away from cTfh2 and cTfh17 cells both toward cTfh1 cells. Importantly, the skewing of Tfh cell subsets correlated with IL-21 and protective antibody titers. Based on the key role of microRNAs involved in Tfh cell differentiation, we revealed miR-19b-1 and miR-92a-1 correlated with the cTfh cell subsets distribution and antibody production.ConclusionsOur findings highlighted a decrease in cTfh cells and specific subset skewing contribute to reduced antibody responses in low responders.

Highlights

There are 3.5 % of the global people chronically infected with hepatitis B virus (HBV), resulting in cirrhosis complications and hepatic carcinoma (Hutin et al 2018; Yuen et al 2018)
A skewed circulating follicular helper T (cTfh) population away from cTfh2 and cTfh17 toward cTfh1 in the low responders to hepatitis B vaccine Given the growing recognition of the different capacities of T follicular helper (Tfh) cell subsets in supporting antibody secretion, we further explore whether distribution of specialized cTfh subsets contributes to the low responsiveness to hepatitis B vaccine
PD1+ICOS+Tfh2 cells were induced after human papillomavirus vaccination (Matsui et al 2015)and the Tfh17 cell subset was induced during the antibody response to rVSV-ZEBOV Ebola vaccine (Farooq et al 2016)

Summary

Introduction

There are 3.5 % of the global people chronically infected with hepatitis B virus (HBV), resulting in cirrhosis complications and hepatic carcinoma (Hutin et al 2018; Yuen et al 2018). As hepatitis B vaccination has been widely available across the world over recent decades, incidence of HBV infections is decreasing. T follicular helper (Th) and Th2 cells have been considered to predominantly regulate the poor immune response to hepatitis B vaccination, but still with controversial results (Larsen et al 2000; Wataya et al 2001). Yin et al Mol Med (2021) 27:32 evidence suggests that T follicular helper (Tfh) cell-the major helper T cell subset are instrumental in humoral adaptive immune response. Little is known about the part of Tfh cells and subsets in low-responsiveness to hepatitis B vaccination. An estimated 5–10 % of healthy vaccinees lack adequate antibody response following receipt of a standard three-dose hepatitis B vaccination regimen. The cellular mechanisms responsible for poor immunological responses to hepatitis B vaccine have not been fully elucidated to date

Methods

Discussion

Conclusion