Title |
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
|
---|---|
Published in |
Frontiers in Cellular and Infection Microbiology, January 2018
|
DOI | 10.3389/fcimb.2018.00006 |
Pubmed ID | |
Authors |
Julien Revaud, Yves Unterfinger, Nicolas Rol, Muhammad Suleman, Julia Shaw, Sandra Galea, Françoise Gavard, Sandrine A. Lacour, Muriel Coulpier, Nicolas Versillé, Menzo Havenga, Bernard Klonjkowski, Gina Zanella, Stéphane Biacchesi, Nathalie Cordonnier, Blaise Corthésy, Juliette Ben Arous, Jennifer P. Richardson |
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. |
X Demographics
As of 1 July 2024, you may notice a temporary increase in the numbers of X profiles with Unknown location. Click here to learn more.
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 50% |
Scientists | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 12 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 5 | 42% |
Student > Ph. D. Student | 2 | 17% |
Unspecified | 2 | 17% |
Professor > Associate Professor | 1 | 8% |
Student > Master | 1 | 8% |
Other | 0 | 0% |
Unknown | 1 | 8% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 4 | 33% |
Unspecified | 2 | 17% |
Veterinary Science and Veterinary Medicine | 1 | 8% |
Biochemistry, Genetics and Molecular Biology | 1 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 8% |
Other | 2 | 17% |
Unknown | 1 | 8% |