Generation and characterization of a novel candidate gene therapy and vaccination vector based on human species D adenovirus type 56

Duffy, M. R. et al. (2018) Generation and characterization of a novel candidate gene therapy and vaccination vector based on human species D adenovirus type 56. Journal of General Virology, 99(1), pp. 135-147. (doi: 10.1099/jgv.0.000978) (PMID:29154744)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Baker, Professor Andrew and Alonso Padilla, Dr Julio
Authors: Duffy, M. R., Alonso-Padilla, J., John, L., Chandra, N., Khan, S., Ballmann, M. Z., Lipiec, A., Heemskerk, E., Custers, J., Arnberg, N., Havenga, M., Baker, A. H., and Lemckert, A.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Journal of General Virology
Publisher:Microbiology Society
ISSN (Online):1465-2099
Published Online:20 November 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Journal of General Virology 99(1):135-147
Publisher Policy:Reproduced under a Creative Commons License

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