ArticlePloS one2011
DNA immunization with fusion of CTLA-4 to hepatitis B virus (HBV) core protein enhanced Th2 type responses and cleared HBV with an accelerated kinetic.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Nucleotides Entrapped in Liposome Nanovesicles as Tools for Therapeutic and Diagnostic Use in Biomedical Applications.Pharmaceutics · 2023Review
- Bioinformatics-based design of a fusion vaccine with CTLA-4 variable region to combat Brucella.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023Article
- Identification of key genes and pathways associated with different immune statuses of hepatitis B virus infection.Journal of cellular and molecular medicine · 2019Article
- Therapeutic DNA Vaccines for Human Papillomavirus and Associated Diseases.Human gene therapy · 2018Article
- CTLA‑4 interferes with the HBV‑specific T cell immune response (Review).International journal of molecular medicine · 2018Review
- The IL-1R/TLR signaling pathway is essential for efficient CD8Cellular & molecular immunology · 2017Article
- The dose of HBV genome contained plasmid has a great impact on HBV persistence in hydrodynamic injection mouse model.Virology journal · 2017Article
- Article
- Construction of a fusion plasmid containing the PSCA gene and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and its anti-tumor effect in an animal model of prostate cancer.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2016Article
- Characterization of the Treg Response in the Hepatitis B Virus Hydrodynamic Injection Mouse Model.PloS one · 2016Article
- IL-33 Enhances Humoral Immunity Against Chronic HBV Infection Through Activating CD4(+)CXCR5(+) TFH Cells.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2015Article
- [Immune modulation treatment of chronic hepatitis B virus infection].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2015Article
- Persistence of the recombinant genomes of woodchuck hepatitis virus in the mouse model.PloS one · 2015Article
- Coexistence of hepatitis B virus quasispecies enhances viral replication and the ability to induce host antibody and cellular immune responses.Journal of virology · 2014Article
- Fusion of CTLA-4 with HPV16 E7 and E6 enhanced the potency of therapeutic HPV DNA vaccine.PloS one · 2014Article
- Immunosuppressive drugs modulate the replication of hepatitis B virus (HBV) in a hydrodynamic injection mouse model.PloS one · 2014Article
- DNA vaccine cocktail expressing genotype A and C HBV surface and consensus core antigens generates robust cytotoxic and antibody responses in mice and Rhesus macaques.Cancer gene therapy · 2013Article
- Potentiating functional antigen-specific CD8⁺ T cell immunity by a novel PD1 isoform-based fusion DNA vaccine.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Inhibition of hepatitis B virus (HBV) gene expression and replication by HBx gene silencing in a hydrodynamic injection mouse model with a new clone of HBV genotype B.Virology journal · 2013Article
- Influence of the oncolytic parvovirus H-1, CTLA-4 antibody tremelimumab and cytostatic drugs on the human immune system in a human in vitro model of colorectal cancer cells.OncoTargets and therapy · 2013Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTypically, DNA immunization via the intramuscular route induces specific, Th1-dominant immune responses. However, plasmids expressing viral proteins fused to cytotoxic T lymphocyte antigen 4 (CTLA-4) primed Th2-biased responses and were able to induced effective protection against viral challenge in the woodchuck model. Thus, we addressed the question in the mouse model how the Th1/Th2 bias of primed immune responses by a DNA vaccine influences hepatitis B virus (HBV) clearance. PRINCIPAL
findingsPlasmids expressing HBV core protein (HBcAg) or HBV e antigen and HBcAg fused to the extracellular domain of CTLA-4 (pCTLA-4-HBc), CD27, and full length CD40L were constructed. Immunizations of these DNA plasmids induced HBcAg-specific antibody and cytotoxic T-cell responses in mice, but with different characteristics regarding the titers and subtypes of specific antibodies and intensity of T-cell responses. The plasmid pHBc expressing HBcAg induced an IgG2a-dominant response while immunizations of pCTLA-4-HBc induced a balanced IgG1/IgG2a response. To assess the protective values of the immune responses of different characteristics, mice were pre-immunized with pCTLA-4-HBc and pHBc, and challenged by hydrodynamic injection (HI) of pAAV/HBV1.2. HBV surface antigen (HBsAg) and DNA in peripheral blood and HBcAg in liver tissue were cleared with significantly accelerated kinetics in both groups. The clearance of HBsAg was completed within 16 days in immunized mice while more than 50% of the control mice are still positive for HBsAg on day 22. Stronger HBcAg-specific T-cell responses were primed by pHBc correlating with a more rapid decline of HBcAg expression in liver tissue, while anti-HBs antibody response developed rapidly in the mice immunized with pCTLA-4-HBc, indicating that the Th1/Th2 bias of vaccine-primed immune responses influences the mode of viral clearance.
conclusionViral clearance could be efficiently achieved by Th1/Th2-balanced immune response, with a small but significant shift in T-cell and B-cell immune responses.
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