This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lecollinet, S.
Right arrow Articles by Richardson, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lecollinet, S.
Right arrow Articles by Richardson, J.

 Previous Article  |  Next Article 

Journal of Virology, March 2006, p. 2747-2759, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2747-2759.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Improved Gene Delivery to Intestinal Mucosa by Adenoviral Vectors Bearing Subgroup B and D Fibers

S. Lecollinet,1 F. Gavard,1 M. J. E. Havenga,2 O. B. Spiller,3 A. Lemckert,2 J. Goudsmit,2 M. Eloit,1 and J. Richardson1*

UMR01161 ENVA-INRA-AFSSA de Virologie, Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons-Alfort, France,1 CRUCELL Holland BV, 2301 CA Leiden, The Netherlands,2 Virus Receptor and Immune Evasion Group, Department of Child Health, Cardiff University, Wales School of Medicine, Fifth Floor Heath Hospital, Health Park, Cardiff CF4 4XN, United Kingdom3

Received 13 October 2005/ Accepted 15 December 2005

A major obstacle to successful oral vaccination is the lack of antigen delivery systems that are both safe and highly efficient. Conventional replication-incompetent adenoviral vectors, derived from human adenoviruses of subgroup C, are poorly efficient in delivering genetic material to differentiated intestinal epithelia. To date, 51 human adenovirus serotypes have been identified and shown to recognize different cellular receptors with different tissue distributions. This natural diversity was exploited in the present study to identify suitable adenoviral vectors for efficient gene delivery to the human intestinal epithelium. In particular, we compared the capacities of a library of adenovirus type 5-based vectors pseudotyped with fibers of several human serotypes for transduction, binding, and translocation toward the basolateral pole in human and murine tissue culture models of differentiated intestinal epithelia. In addition, antibody-based inhibition was used to gain insight into the molecular interactions needed for efficient attachment. We found that vectors differing merely in their fiber proteins displayed vastly different capacities for gene transfer to differentiated human intestinal epithelium. Notably, vectors bearing fibers derived from subgroup B and subgroup D serotypes transduced the apical pole of human epithelium with considerably greater efficiency than a subgroup C vector. Such efficiency was correlated with the capacity to use CD46 or sialic acid-containing glycoconjugates as opposed to CAR as attachment receptors. These results suggest that substantial gains could be made in gene transfer to digestive epithelium by exploiting the tropism of existing serotypes of human adenoviruses.

* Corresponding author. Mailing address: ENVA, UMR01161 de Virologie, 7 Avenue du Général de Gaulle, 94704 Maisons-Alfort, France. Phone: 33 (0)1 43 96 73 71. Fax: 33 (0)1 43 96 73 96. E-mail: jrichardson{at}vet-alfort.fr.

Journal of Virology, March 2006, p. 2747-2759, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2747-2759.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Szelechowski, M., Fournier, A., Richardson, J., Eloit, M., Klonjkowski, B. (2009). Functional organization of the major late transcriptional unit of canine adenovirus type 2. J. Gen. Virol. 90: 1215-1223 [Abstract] [Full Text]  
  • Russell, W. C. (2009). Adenoviruses: update on structure and function. J. Gen. Virol. 90: 1-20 [Abstract] [Full Text]  
  • Parker, A. L., McVey, J. H., Doctor, J. H., Lopez-Franco, O., Waddington, S. N., Havenga, M. J. E., Nicklin, S. A., Baker, A. H. (2007). Influence of Coagulation Factor Zymogens on the Infectivity of Adenoviruses Pseudotyped with Fibers from Subgroup D. J. Virol. 81: 3627-3631 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»