Generation and characterization of a novel candidate gene therapy and vaccination vector based on human species D adenovirus type 56
| Autor: | Evert Heemskerk, Jerome Custers, Selina Khan, Lijo John, Menzo J. E. Havenga, Agnieszka Lipiec, Mónika Z. Ballmann, Naresh Chandra, Niklas Arnberg, Margaret R. Duffy, Andy Baker, Julio Alonso-Padilla, Angelique A. C. Lemckert |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Candidate gene vaccine vector Genetic enhancement Gene Expression Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology) Molecular Biology Microbiology Biochemistry or Biopharmacy) Antibodies Viral Chemokine CXCL9 law.invention Mice Transduction (genetics) law Transgenes Lung Chemokine CCL2 Mice Inbred BALB C biology Vaccination virus diseases adenovirus gene therapy 3. Good health Injections Intravenous Recombinant DNA Female Antibody HAdV-56 Genetic Vectors Microbiology in the medical area Interferon-gamma 03 medical and health sciences Immune system In vivo Virology Mikrobiologi inom det medicinska området Animals Humans Luciferase Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi) molekylärbiologi mikrobiologi biokemi eller biofarmaci) Interleukin-6 Tumor Necrosis Factor-alpha Adenoviruses Human Viral Vaccines Genetic Therapy eye diseases Chemokine CXCL10 030104 developmental biology biology.protein Interleukin-5 Spleen |
| Zdroj: | Journal of General Virology. 99:135-147 |
| ISSN: | 1465-2099 0022-1317 |
| Popis: | The vectorization of rare human adenovirus (HAdV) types will widen our knowledge of this family and their interaction with cells, tissues and organs. In this study we focus on HAdV-56, a member of human Ad species D, and create ease-of-use cloning systems to generate recombinant HAdV-56 vectors carrying foreign genes. We present in vitro transduction profiles for HAdV-56 in direct comparison to the most commonly used HAdV-5-based vector. In vivo characterizations demonstrate that when it is delivered intravenously (i.v.) HAdV-56 mainly targets the spleen and, to a lesser extent, the lungs, whilst largely bypassing liver transduction in mice. HAdV-56 triggered robust inflammatory and cellular immune responses, with higher induction of IFNγ, TNFα, IL5, IL6, IP10, MCP1 and MIG1 compared to HAdV-5 following i.v. administration. We also investigated its potential as a vaccine vector candidate by performing prime immunizations in mice with HAdV-56 encoding luciferase (HAdV-56-Luc). Direct comparisons were made to HAdV-26, a highly potent human vaccine vector currently in phase II clinical trials. HAdV-56-Luc induced luciferase 'antigen'-specific IFNγ-producing cells and anti-HAdV-56 neutralizing antibodies in Balb/c mice, demonstrating a near identical profile to that of HAdV-26. Taken together, the data presented provides further insight into human Ad receptor/co-receptor usage, and the first report on HAdV-56 vectors and their potential for gene therapy and vaccine applications. |
| Databáze: | OpenAIRE |
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