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
| Autor: | 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 |
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| Přispěvatelé: | Virologie UMR1161 (VIRO), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Université Paris Est, Société d'Exploitation de Produits pour les Industries Chimiques (SEPPIC), Centre Hospitalier Universitaire Vaudois (CHUV), Batavia Biosci BV, Leiden, Netherlands, Partenaires INRAE, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Université Paris Saclay (COmUE), French national institute for agricultural research (INRA), SEPPIC, Animal Health department of INRA, Higher Education Commission of Pakistan, Ile de France region (Domaine d'interet majeur 'Maladies infectieuses, parasitaires et nosocomiales emergentes'), Swiss government, French government, Swiss National Science Foundation (SNF) [3100-156806], Richardson, Jennifer |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
[SDV]Life Sciences [q-bio] lcsh:QR1-502 Administration Oral Gene Expression Adenoviruses Human/genetics Adenoviruses Human/immunology Animals Female Genes Reporter Genetic Vectors/administration & dosage Genetic Vectors/genetics Genetic Vectors/immunology Humans Immunization Intestinal Mucosa/immunology Intestinal Mucosa/metabolism Mice Organ Specificity Peyer's Patches/immunology Peyer's Patches/metabolism Phagocytes/metabolism Protein Transport Transgenes/genetics Transgenes/immunology Vaccination M cell Peyer's patch adenovirus oral vaccination viral vector lcsh:Microbiology Peyer's Patches 0302 clinical medicine Intestinal mucosa Vector (molecular biology) Transgenes Intestinal Mucosa Microfold cell Original Research Phagocytes Intestinal epithelium 3. Good health Cell biology Infectious Diseases medicine.anatomical_structure Microbiology (medical) Immunology Genetic Vectors Biology Microbiology Viral vector 03 medical and health sciences Antigen medicine Adenoviruses Human Epithelium 030104 developmental biology 030215 immunology |
| Zdroj: | Frontiers in Cellular and Infection Microbiology Frontiers in Cellular and Infection Microbiology, Frontiers, 2018, 8, pp.1-15. ⟨10.3389/fcimb.2018.00006⟩ Frontiers in Cellular and Infection Microbiology (8), 1-15. (2018) Frontiers in Cellular and Infection Microbiology, Vol 8 (2018) Frontiers in cellular and infection microbiology, vol. 8, pp. 6 |
| ISSN: | 2235-2988 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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