Circulating Tfh cell and subsets distribution are associated with low-responsiveness to hepatitis B vaccination

Mol Med. 2021 Apr 1;27(1):32. doi: 10.1186/s10020-021-00290-7.


Background: 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: There 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.

Results: We 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.

Conclusions: Our findings highlighted a decrease in cTfh cells and specific subset skewing contribute to reduced antibody responses in low responders.

Keywords: Circulating Tfh cells; Hepatitis B vaccination; Low‐responsiveness; miR-19b-1; miR-92a-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / blood*
  • Female
  • Hepatitis B / immunology*
  • Hepatitis B Vaccines*
  • Humans
  • Interleukins / blood*
  • Male
  • MicroRNAs*
  • T Follicular Helper Cells / immunology*
  • Vaccination
  • Young Adult


  • Antibodies, Viral
  • Hepatitis B Vaccines
  • Interleukins
  • MicroRNAs
  • interleukin-21