Booster immunization improves the generation of T follicular helper (Tfh) cells specific to hepatitis B surface antigen (HBsAg) after prenatal HBsAg exposure

Breakthrough infections of hepatitis B virus (HBV) after neonatal vaccination occurred in some adolescents and young adults who were born to mothers with hepatitis B surface antigen (HBsAg). We aimed to determine the impacts of prenatal HBsAg exposure on the generation of T follicular helper (Tfh) cells and antibodies (anti-HBs) specific to HBsAg. To mimic human prenatal HBsAg exposure, we mated female Alb1-HBV (HBV-M) mice with male C57BL/6J mice. Of their first filial generation (F1), HBV-M/F1' expressed HBsAg in liver tissues and blood, and HBV-M/F1- mice exposed HBsAg in amniotic fluid. At their four weeks old, each HBV-M/F1 mouse was immunized with hepatitis B vaccine containing 5 lg HBsAg subcutaneously. Both HBV-M/F1- and HBV-M/F1' mice had reduced generation of HBsAg-specific CD4'CXCR5'PD1' Tfh cells and CD138'IgD- plasma cells in comparison with C57BL/6J mice. Results of coculturing the Tfh cells with B cells that were isolated from different strains of mice indicated that CD4' T cell activation in response to HBsAg was critical for anti-HBs generation after prenatal HBsAg exposure. When interleukin (IL) 21 was supplemented, the generation of HBsAg-specific Tfh and plasma cells in HBV-M/F1- mice was improved, while supplementation showed little effect in HBV-M/F1' mice. In HBV-M/F1- mice, HBV vaccine booster improved the generation of Tfh cells and plasma cells, and enhanced anti-HBs production. Conclusion: Impaired generation of HBsAg-specific Tfh cells and plasma cells after prenatal HBsAg exposure can be improved by HBV vaccine booster, most likely increasing IL-21 production. (C) 2021 Elsevier Ltd. All rights reserved.