Open AccessChanges in Innate and Permissive Immune Responses after HBV Transgenic Mouse Vaccination and lLong-Term-siRNA Treatment
Author(s) -
Guangli Ren,
GuiFang Huang,
Hong Zheng,
Yīng Fāng,
Heng-Hao Ma,
Man-Chun Xu,
Hongbin Zhang,
Weiyun Zhang,
Yong Zhao,
Desheng Sun,
Wen-Kui Hu,
Jian Liu
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0057525
Subject(s) - hbsag , hepatitis b virus , immune system , virology , small interfering rna , immunology , cpg oligodeoxynucleotide , interferon , hbeag , vaccination , biology , medicine , hepatitis b , virus , transfection , cell culture , biochemistry , genetics , dna methylation , gene , gene expression
Background Currently, no licensed therapy can thoroughly eradicate hepatitis B virus (HBV) from the body, including interferon α and inhibitors of HBV reverse-transcription. Small interfering RNA (siRNA) seem to be a promising tool for treating HBV, but had no effect on the pre-existing HBV covalently closed circular DNA. Because it is very difficult to thoroughly eradicate HBV with unique siRNAs, upgrading the immune response is the best method for fighting HBV infection. Here, we aim to explore the immune response of transgenic mice to HBV vaccination after long-term treatment with siRNAs and develop a therapeutic approach that combines siRNAs with immunopotentiators. Methodology/Principal Findings To explore the response of transgenic mice to hepatitis B vaccine, innate and acquired immunity were detected after long-term treatment with siRNAs and vaccination. Antiviral cytokines and level of anti-hepatitis B surface antigen antibody (HBsAg-Ab) were measured after three injections of hepatitis B vaccine. Results Functional analyses indicated that toll-like receptor-mediated innate immune responses were reinforced, and antiviral cytokines were significantly increased, especially in the pSilencer4.1/HBV groups. Analysis of CD80+/CD86+ dendritic cells in the mouse liver indicated that dendritic cell antigen presentation was strengthened. Furthermore, the siRNA-treated transgenic mice could produce detectable HBsAg-Ab after vaccination, especially in the CpG oligonucleotide vaccine group. Conclusions/Significance For the first time, our studies demonstrate that siRNAs with CpG HBV vaccine could strengthen the immune response and break the immune tolerance status of transgenic mice to HBV. Thus, siRNAs and HBV vaccine could provide a sharp double-edged sword against chronic HBV infection.