<i>In vitro</i> and <i>in vivo</i> tropism and biodistribution of recombinant simian adenovirus type 25

Abstract

Introduction. Recombinant adenoviruses are widely used in the development of vaccines for a variety of infectious diseases. Despite numerous clinical studies, only a few types of human (types 5 and 26) and simian (isolate Y25) adenoviruses are currently used to produce vaccine formulations. Different types of adenoviruses vary in their cellular tropism, which plays a key role in their ability to elicit an immune response. The aim of this study was to investigate the cellular tropism of the simian adenovirus type 25 in vitro and its biodistribution in vivo in comparison with human adenoviruses types 5 and 26. Materials and methods. The efficiency of in vitro transduction was evaluated on 15 different cell lines using recombinant adenovirus vectors expressing the enhanced green fluorescent protein (EGFP) reporter gene. In vivo biodistribution and bioluminescence imaging were evaluated in BALB/c mice after administration of recombinant adenoviral vectors encoding the luciferase reporter gene. The acute toxicity of a recombinant simian adenovirus type 25 vector was assessed in mice and rats following intramuscular or intravenous administration. Results. Recombinant simian adenovirus effectively transduces a wide range of cells. At the same time, a higher tropism to human glioblastoma cells (GL-6) was found compared to the other two studied adenoviruses. In vivo experiments have shown that recombinant adenoviruses are mainly localized at the injection site, and transgene expression persists for 21 days. Acute toxicity studies demonstrated that simian adenovirus type 25 vector was well-tolerated, with no animal deaths or detectable toxic effects. Conclusion. The new platform based on the recombinant simian adenovirus type 25 is not inferior to the existing and well-established delivery systems based on human adenovirus types 5 and 26. Due to its high level of gene transfer and favorable safety profile, the use of the simian adenovirus type 25 in medicine has the potential to offer many benefits for the development of vaccines against future infectious diseases.