Skip to Main content Skip to Navigation
Journal articles

Firewalls prevent systemic dissemination of vectors derived from human adenovirus type 5 and suppress production of transgene-encoded antigen in a murine model of oral vaccination

Abstract : To define the bottlenecks that restrict antigen expression after oral administration of viral-vectored vaccines, we tracked vectors derived from the human adenovirus type 5 at whole body, tissue, and cellular scales throughout the digestive tract in a murine model of oral delivery. After intragastric administration of vectors encoding firefly luciferase or a model antigen, detectable levels of transgene-encoded protein or mRNA were confined to the intestine, and restricted to delimited anatomical zones. Expression of luciferase in the form of multiple small bioluminescent foci in the distal ileum, cecum, and proximal colon suggested multiple crossing points. Many foci were unassociated with visible Peyer's patches, implying that transduced cells lay in proximity to villous rather than follicle-associated epithelium, as supported by detection of transgene-encoded antigen in villous epithelial cells. Transgene-encoded mRNA but not protein was readily detected in Peyer's patches, suggesting that post-transcriptional regulation of viral gene expression might limit expression of transgene-encoded antigen in this tissue. To characterize the pathways by which the vector crossed the intestinal epithelium and encountered sentinel cells, a fluorescent-labeled vector was administered to mice by the intragastric route or inoculated into ligated intestinal loops comprising a Peyer's patch. The vector adhered selectively to microfold cells in the follicle-associated epithelium, and, after translocation to the subepithelial dome region, was captured by phagocytes that expressed CD11c and lysozyme. In conclusion, although a large number of crossing events took place throughout the intestine within and without Peyer's patches, multiple firewalls prevented systemic dissemination of vector and suppressed production of transgene-encoded protein in Peyer's patches.
Document type :
Journal articles
Complete list of metadata

Cited literature [65 references]  Display  Hide  Download

https://hal.inrae.fr/hal-02627246
Contributor : Migration ProdInra Connect in order to contact the contributor
Submitted on : Tuesday, May 26, 2020 - 7:38:30 PM
Last modification on : Tuesday, May 17, 2022 - 3:38:01 PM

File

2018_Revaud_Frontiers in Cellu...
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Citation

Julien Revaud, Yves Unterfinger, Nicolas Rol, Muhammad Suleman, Julia Shaw, et al.. Firewalls prevent systemic dissemination of vectors derived from human adenovirus type 5 and suppress production of transgene-encoded antigen in a murine model of oral vaccination. Frontiers in Cellular and Infection Microbiology, Frontiers, 2018, 8, pp.1-15. ⟨10.3389/fcimb.2018.00006⟩. ⟨hal-02627246⟩

Share

Metrics

Record views

22

Files downloads

11