The Biodistribution of Replication-Defective Simian Adenovirus 1 Vector in a Mouse Model

The administration route affects the biodistribution of a gene transfer vector and the expression of a transgene. A simian adenovirus 1 vector carrying firefly luciferase and GFP reporter genes (SAdV1-GFluc) were constructed, and its biodistribution was investigated in a mouse model by bioluminescen...

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Published in:	Viruses Vol. 16; no. 4; p. 550
Main Authors:	Chen, Juan, Guo, Xiaojuan, Zou, Xiaohui, Wang, Min, Yang, Chunlei, Hou, Wenzhe, Sprindzuk, Matvey V, Lu, Zhuozhuang
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 01-04-2024 MDPI
Subjects:	adenovirus Adenoviruses Adenoviruses, Simian - genetics administration route Administration, Intranasal Animal experimentation Animals Antibodies Antibodies, Neutralizing - immunology biodistribution Bioluminescence bioluminescence imaging Distribution DNA viruses E coli Epithelial cells Female Flow cytometry Gene Expression Gene therapy Gene transfer Genes Genes, Reporter Genetic aspects Genetic vectors Genetic Vectors - genetics Genomes Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism Hepatocytes Humans Identification and classification Immunohistochemistry Infections Injection Injections, Intramuscular Inoculation Intranasal administration Intravenous administration Laboratory animals Large intestine Liver Liver - metabolism Liver - virology Luciferase Luciferases, Firefly - genetics Macrophages Methods Mice Mice, Inbred BALB C Models, Animal Plasmids Reporter gene Respiratory tract simian adenovirus 1 Small intestine Spleen Spleen - metabolism Spleen - virology Testing Tissue Distribution Transduction, Genetic Transgenes Vaccine development Vaccines Vectors (Biology) Viral antibodies Virus Replication Viruses China Beijing China United States > US biodistribution gene transfer mouse model simian adenovirus 1 vectored vaccine adenovirus bioluminescence imaging real-time PCR administration route
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Summary:	The administration route affects the biodistribution of a gene transfer vector and the expression of a transgene. A simian adenovirus 1 vector carrying firefly luciferase and GFP reporter genes (SAdV1-GFluc) were constructed, and its biodistribution was investigated in a mouse model by bioluminescence imaging and virus DNA tracking with real-time PCR. Luciferase activity and virus DNA were mainly found in the liver and spleen after the intravenous administration of SAdV1-GFluc. The results of flow cytometry illustrated that macrophages in the liver and spleen as well as hepatocytes were the target cells. Repeated inoculation was noneffective because of the stimulated serum neutralizing antibodies (NAbs) against SAdV-1. A transient, local expression of low-level luciferase was detected after intragastric administration, and the administration could be repeated without compromising the expression of the reporter gene. Intranasal administration led to a moderate, constant expression of a transgene in the whole respiratory tract and could be repeated one more time without a significant increase in the NAb titer. An immunohistochemistry assay showed that respiratory epithelial cells and macrophages in the lungs were transduced. High luciferase activity was restricted at the injection site and sustained for a week after intramuscular administration. A compromised transgene expression was observed after a repeated injection. When these mice were intramuscularly injected for a third time with the human adenovirus 5 (HAdV-5) vector carrying a luciferase gene, the luciferase activity recovered and reached the initial level, suggesting that the sequential use of SAdV-1 and HAdV-5 vectors was practicable. In short, the intranasal inoculation or intramuscular injection may be the preferred administration routes for the novel SAdV-1 vector in vaccine development.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1999-4915 1999-4915
DOI:	10.3390/v16040550