Unknown

Dataset Information

0

Sustained Liver HBsAg Loss and Clonal T- and B-Cell Expansion upon Therapeutic DNA Vaccination Require Low HBsAg Levels.


ABSTRACT:

Background

Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a GalNAc-HBV-siRNA followed by therapeutic vaccination.

Methods

AAV-HBV-transduced C57BL/6 mice were treated with GalNAc-HBV-siRNA to lower HBsAg levels and then vaccinated using a DNA vaccine. We used single-cell RNA and V(D)J sequencing to understand liver immune microenvironment changes.

Results

GalNAc-HBV-siRNA, followed by therapeutic vaccination, achieved sustained HBsAg loss in all mice. This was accompanied by CD4 follicular helper T-cell induction, polyclonal activation of CD8 T cells and clonal expansion of plasma cells that were responsible for antibody production.

Conclusions

This study provides novel insights into liver immune changes at the single-cell level, highlighting the correlation between induced reduction of HBsAg levels and clonal expansion of CD4, CD8 T cells and plasma cells in the liver upon HBV siRNA and subsequent therapeutic vaccination.

SUBMITTER: Conceicao-Neto N 

PROVIDER: S-EPMC10747285 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications


<h4>Background</h4>Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a  ...[more]

Similar Datasets

| S-EPMC5645387 | biostudies-literature
2024-04-28 | GSE230863 | GEO
2024-04-28 | GSE230861 | GEO
2024-04-28 | GSE230862 | GEO
| S-EPMC5503750 | biostudies-literature
| S-EPMC9933345 | biostudies-literature
| S-EPMC9980474 | biostudies-literature
| S-EPMC5316831 | biostudies-literature
| S-EPMC1087520 | biostudies-literature
| S-EPMC11485260 | biostudies-literature