Abstract
BackgroundA therapeutic vaccine for chronic hepatitis B virus (HBV) infection that enhances virus-specific cellular immune responses is urgently needed. The “prime–boost” regimen is a widely used vaccine strategy against many persistence infections. However, few reports have addressed this strategy applying for HBV therapeutic vaccine development.Methodology/Principal FindingsTo develop an effective HBV therapeutic vaccine, we constructed a recombinant vaccinia virus (Tiantan) containing the S+PreS1 fusion antigen (RVJSS1) combined with the HBV particle-like subunit vaccine HBVSS1 to explore the most effective prime–boost regimen against HBV. The immune responses to different prime–boost regimens were assessed in C57BL/C mice by ELISA, ELISpot assay and Intracellular cytokine staining analysis. Among the combinations tested, an HBV protein particle vaccine priming and recombinant vaccinia virus boosting strategy accelerated specific seroconversion and produced high antibody (anti-PreS1, anti-S antibody) titres as well as the strongest multi-antigen (PreS1, and S)-specific cellular immune response. HBSS1 protein prime/RVJSS1 boost immunization was also generated more significant level of both CD4+ and CD8+ T cell responses for Th1 cytokines (TNF-α and IFN-γ).ConclusionsThe HBSS1 protein-vaccine prime plus RVJSS1 vector boost elicits specific antibody as well as CD4 and CD8 cells secreting Th1-like cytokines, and these immune responses may be important parameters for the future HBV therapeutic vaccines.
Highlights
Hepatitis B virus (HBV) infection is a major global health problem
The HBSS1 protein-vaccine prime plus RVJSS1 vector boost elicits specific antibody as well as CD4 and CD8 cells secreting Th1-like cytokines, and these immune responses may be important parameters for the future hepatitis B virus (HBV) therapeutic vaccines
The recombinant vaccinia virus RVJSS1 expressing HBV S and PreS1 fusion proteins was developed by homologous recombination in chick embryo fibroblast (CEF) cells with the shuttle plasmid pJSA1175-SS1 and the parent virus TTV
Summary
Hepatitis B virus (HBV) infection is a major global health problem. An estimated 2 billion people worldwide have been infected with the virus, and approximately 350 million are chronically infected that may lead to liver cirrhosis and hepatocellular carcinoma, causing 600,000 deaths per year [1]. The current vaccination protocol recommends two to three doses to induce long-lasting immunity, and even after completion of the full HBV vaccine regimen, up to 10% of the population is unable generate a protective response to the virus [6]. Currently used antiviral therapies, including treatment with pegylated interferon alpha 2a (PEGIFN2a) or nucleos(t)ide analogues such as lamivudine [8,9], significantly suppress HBV replication, they cannot completely eradicate the virus and can cause severe adverse reactions. A therapeutic vaccine for chronic hepatitis B that enhances virus-specific immune responses and overcomes persistent HBV infection is urgently needed. A therapeutic vaccine for chronic hepatitis B virus (HBV) infection that enhances virus-specific cellular immune responses is urgently needed. Few reports have addressed this strategy applying for HBV therapeutic vaccine development
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
