ArticleGene therapy2003
Low dose and gene gun immunization with a hepatitis C virus nonstructural (NS) 3 DNA-based vaccine containing NS4A inhibit NS3/4A-expressing tumors in vivo.
Article in Gene therapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Hepatitis C virus DNA vaccines: a systematic review.Virology journal · 2021Pooled it
- Minicircle-based vaccine induces potent T-cell and antibody responses against hepatitis C virus.Scientific reports · 2024Article
- In the era of rapid mRNA-based vaccines: Why is there no effective hepatitis C virus vaccine yet?World journal of hepatology · 2021Review
- Article
- Functional differences in hepatitis C virus nonstructural (NS) 3/4A- and 5A-specific T cell responses.Scientific reports · 2016Article
- A targeted controlled force injection of genetic material in vivo.Molecular therapy. Methods & clinical development · 2016Article
- Expression of NS3/NS4A Proteins of Hepatitis C Virus in Huh7 Cells Following Engineering Its Eukaryotic Expression Vector.Jundishapur journal of microbiology · 2015Article
- A Multiantigenic DNA Vaccine That Induces Broad Hepatitis C Virus-Specific T-Cell Responses in Mice.Journal of virology · 2015Article
- Article
- Long-term functional duration of immune responses to HCV NS3/4A induced by DNA vaccination.Gene therapy · 2014Article
- Short noncoding DNA fragments improve the immune potency of electroporation-mediated HBV DNA vaccination.Gene therapy · 2014Article
- Immunocompetent mouse models to evaluate intrahepatic T cell responses to HCV vaccines.Human vaccines & immunotherapeutics · 2014Article
- Coupling to the surface of liposomes alters the immunogenicity of hepatitis C virus-derived peptides and confers sterile immunity.Biochemical and biophysical research communications · 2013Article
- Construction and preparation of three recombinant adenoviruses expressing truncated NS3 and core genes of hepatitis C virus for vaccine purposes.Hepatitis monthly · 2012Article
- Generation of T-cell receptors targeting a genetically stable and immunodominant cytotoxic T-lymphocyte epitope within hepatitis C virus non-structural protein 3.The Journal of general virology · 2012Article
- Engineered toxins "zymoxins" are activated by the HCV NS3 protease by removal of an inhibitory protein domain.PloS one · 2011Article
- Temperature-assisted cyclic hybridization (TACH): an improved method for supercoiled DNA hybridization.Molecular biotechnology · 2010Article
- Article
- The hepatitis C virus non-structural NS5A protein impairs both the innate and adaptive hepatic immune response in vivo.The Journal of biological chemistry · 2009Article
- Interaction of the hepatitis B core antigen and the innate immune system.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatitis C virus (HCV) protease and helicase encompasses the nonstructural (NS) 3 protein and the cofactor NS4A, which targets the NS3/4A-complex to intracellular membranes. We here evaluate the importance of NS4A in NS3-based genetic immunogens. A full-length genotype 1 NS3/4A gene was cloned into a eucaryotic expression vector in the form of NS3/4A and NS3 alone. Transient transfections revealed that the inclusion of NS4A increased the expression levels of NS3. Subsequently, immunization with the NS3/4A gene primed 10- to 100-fold higher levels of NS3-specific antibodies as compared to immunization with the NS3 gene. Humoral responses primed by the NS3/4A gene had a higher IgG2a/IgG1 ratio (>20) as compared to the NS3 gene (3.0), suggesting a T helper 1-skewed response. Low dose i.m. (10 microg) immunization with the NS3/4A gene inhibited the growth of NS3/4A-expressing tumor cells in vivo, whereas the NS3 gene alone or NS3 protein did not. We then evaluated the efficiency of the NS3/4A gene administered by the gene gun, at the same doses used for humans, in priming cytotoxic T lymphocyte (CTL) responses. Three to four 4 microg doses of the NS3/4A gene primed CTL at a precursor frequency of 2-4%, which inhibited the growth of NS3/4A-expressing tumor cells in vivo. Thus, NS4A enhances the expression levels and immunogenicity of NS3, and an NS3/4A gene delivered transdermally could be a therapeutic vaccine candidate.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.