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 Hong, S. S.
Right arrow Articles by Boulanger, P. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hong, S. S.
Right arrow Articles by Boulanger, P. A.

 Previous Article  |  Next Article 

Journal of Virology, October 2003, p. 10366-10375, Vol. 77, No. 19
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.19.10366-10375.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Identification of Adenovirus (Ad) Penton Base Neutralizing Epitopes by Use of Sera from Patients Who Had Received Conditionally Replicative Ad (Addl1520) for Treatment of Liver Tumors

Saw See Hong,1* Nagy A. Habib,2 Laure Franqueville,1 Steen Jensen,2 and Pierre A. Boulanger1

Laboratoire de Virologie et Pathogénèse Virale, CNRS UMR 5537, Faculté de Médecine and Institut Fédératif de Recherche RTH Laennec, 69372 Lyon, France,1 Department of Surgical Oncology and Technology, Imperial College Faculty of Medicine, Hammersmith Hospital Campus, London W12 0NN, United Kingdom2

Received 26 February 2003/ Accepted 25 June 2003

Sera from 17 patients with primary and secondary liver tumors who had been administered oncolytic adenovirus (Ad) mutant Addl1520 were analyzed for anti-Ad neutralization titers and antibodies to the Ad major capsid proteins hexon, penton base (Pb), and fiber. The antibodies recognized mainly conformational epitopes in hexon and both linear and conformational epitopes in Pb and fiber. Pb-specific antibodies were isolated from serum samples that had been obtained prior to and during the course of the treatment of four of these patients. We found that the Pb antibodies had a significant contribution toward anti-Ad neutralization, and this mainly occurred at the step of virus internalization. The Pb antigenic epitopes were determined by phage biopanning and were mapped to 10 discrete regions, which made up three major immunodominant domains within residues 51 to 120, 193 to 230, and 311 to 408, respectively. One of these domains (residues 311 to 408) overlapped the highly conserved, integrin-binding RGD (Arg-Gly-Asp) motif. The contribution of antibodies directed to RGD and other epitopes in Ad neutralization activity was determined indirectly by using a phage-mediated depletion assay. Our results suggested that circulating RGD antibodies were not prevalent and were poorly neutralizing and that other peptide motifs within residues 51 to 60, 216 to 226, and 311 to 408 in Pb sequence represented major target sites for neutralizing antibodies.

* Corresponding author. Mailing address: Laboratoire de Virologie et, Pathogénèse Virale, CNRS UMR 5537, Faculté de Médecine RTH Laennec, 7, Rue Guillaume Paradin, Lyon Cedex 69372, France. Phone: 33-(0)-4-78-77-86-21. Fax: 33-(0)-4-78-77-87-51. E-mail: hong{at}laennec.univ-lyon1.fr.

Journal of Virology, October 2003, p. 10366-10375, Vol. 77, No. 19
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.19.10366-10375.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Russell, W. C. (2009). Adenoviruses: update on structure and function. J. Gen. Virol. 90: 1-20 [Abstract] [Full Text]  
  • Smith, J. G., Cassany, A., Gerace, L., Ralston, R., Nemerow, G. R. (2008). Neutralizing Antibody Blocks Adenovirus Infection by Arresting Microtubule-Dependent Cytoplasmic Transport. J. Virol. 82: 6492-6500 [Abstract] [Full Text]  
  • Madisch, I., Hofmayer, S., Moritz, C., Grintzalis, A., Hainmueller, J., Pring-Akerblom, P., Heim, A. (2007). Phylogenetic Analysis and Structural Predictions of Human Adenovirus Penton Proteins as a Basis for Tissue-Specific Adenovirus Vector Design. J. Virol. 81: 8270-8281 [Abstract] [Full Text]  
  • Appaiahgari, M. B., Pandey, R. M., Vrati, S. (2007). Seroprevalence of Neutralizing Antibodies to Adenovirus Type 5 among Children in India: Implications for Recombinant Adenovirus-Based Vaccines. CVI 14: 1053-1055 [Abstract] [Full Text]  
  • Krause, A., Joh, J. H., Hackett, N. R., Roelvink, P. W., Bruder, J. T., Wickham, T. J., Kovesdi, I., Crystal, R. G., Worgall, S. (2006). Epitopes expressed in different adenovirus capsid proteins induce different levels of epitope-specific immunity.. J. Virol. 80: 5523-5530 [Abstract] [Full Text]  
  • Toh, M.-L., Hong, S.-S., Loo, F. v. d., Franqueville, L., Lindholm, L., Berg, W. v. d., Boulanger, P., Miossec, P. (2005). Enhancement of Adenovirus-Mediated Gene Delivery to Rheumatoid Arthritis Synoviocytes and Synovium by Fiber Modifications: Role of Arginine-Glycine-Aspartic Acid (RGD)- and Non-RGD-Binding Integrins. J. Immunol. 175: 7687-7698 [Abstract] [Full Text]  
  • Bauer, U., Flunker, G., Bruss, K., Kallwellis, K., Liebermann, H., Luettich, T., Motz, M., Seidel, W. (2005). Detection of Antibodies against Adenovirus Protein IX, Fiber, and Hexon in Human Sera by Immunoblot Assay. J. Clin. Microbiol. 43: 4426-4433 [Abstract] [Full Text]  
  • Sumida, S. M., Truitt, D. M., Lemckert, A. A. C., Vogels, R., Custers, J. H. H. V., Addo, M. M., Lockman, S., Peter, T., Peyerl, F. W., Kishko, M. G., Jackson, S. S., Gorgone, D. A., Lifton, M. A., Essex, M., Walker, B. D., Goudsmit, J., Havenga, M. J. E., Barouch, D. H. (2005). Neutralizing Antibodies to Adenovirus Serotype 5 Vaccine Vectors Are Directed Primarily against the Adenovirus Hexon Protein. J. Immunol. 174: 7179-7185 [Abstract] [Full Text]  
  • Varghese, R., Mikyas, Y., Stewart, P. L., Ralston, R. (2004). Postentry Neutralization of Adenovirus Type 5 by an Antihexon Antibody. J. Virol. 78: 12320-12332 [Abstract] [Full Text]  
  • Tsai, V., Johnson, D. E., Rahman, A., Wen, S. F., LaFace, D., Philopena, J., Nery, J., Zepeda, M., Maneval, D. C., Demers, G. W., Ralston, R. (2004). Impact of Human Neutralizing Antibodies on Antitumor Efficacy of an Oncolytic Adenovirus in a Murine Model. Clin. Cancer Res. 10: 7199-7206 [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»