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 Xin, K.-Q.
Right arrow Articles by Okuda, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xin, K.-Q.
Right arrow Articles by Okuda, K.

 Previous Article  |  Next Article 

Journal of Virology, December 2006, p. 11899-11910, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.00890-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Induction of Robust Immune Responses against Human Immunodeficiency Virus Is Supported by the Inherent Tropism of Adeno-Associated Virus Type 5 for Dendritic Cells{triangledown}

Ke-Qin Xin,1 Hiroaki Mizukami,2 Masashi Urabe,2 Yoshihiko Toda,1 Kaori Shinoda,1 Atsushi Yoshida,1 Kenji Oomura,1 Yoshitsugu Kojima,1 Motohide Ichino,3 Dennis Klinman,4 Keiya Ozawa,2 and Kenji Okuda1*

Departments of Molecular Biodefense Research,1 Immunology,Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan,3 Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical School, Tochigi-ken 329-0498, Japan,2 Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland 208924

Received 2 May 2006/ Accepted 11 September 2006

The ability of adeno-associated virus serotype 1 to 8 (AAV1 to AAV8) vectors expressing the human immunodeficiency virus type 1 (HIV-1) Env gp160 (AAV-HIV) to induce an immune response was evaluated in BALB/c mice. The AAV5 vector showed a higher tropism for both mouse and human dendritic cells (DCs) than did the AAV2 vector, whereas other AAV serotype vectors transduced DCs only poorly. AAV1, AAV5, AAV7, and AAV8 were more highly expressed in muscle cells than AAV2. An immunogenicity study of AAV serotypes indicates that AAV1, AAV5, AAV7, and AAV8 vectors expressing the Env gp160 gene induced higher HIV-specific humoral and cell-mediated immune responses than the AAV2 vector did, with the AAV5 vector producing the best responses. Furthermore, mice injected with DCs that had been transduced ex vivo with an AAV5 vector expressing the gp160 gene elicited higher HIV-specific cell-mediated immune responses than did DCs transduced with AAV1 and AAV2 vectors. We also found that AAV vectors produced by HEK293 cells and insect cells elicit similar levels of antigen-specific immune responses. These results demonstrate that the immunogenicity of AAV vectors depends on their tropism for both antigen-presenting cells (such as DCs) and non-antigen-presenting cells (such as muscular cells) and that AAV5 is a better vector than other AAV serotypes. These results may aid in the development of AAV-based vaccine and gene therapy.

* Corresponding author. Mailing address: Department of Molecular Biodefense Research, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. Phone: 81(45)787-2602. Fax: 81 (45)787-2851. E-mail: kokuda{at}med.yokohama-cu.ac.jp.

{triangledown} Published ahead of print on 27 September 2006.

Journal of Virology, December 2006, p. 11899-11910, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.00890-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lin, J., Calcedo, R., Vandenberghe, L. H., Bell, P., Somanathan, S., Wilson, J. M. (2009). A New Genetic Vaccine Platform Based on an Adeno-Associated Virus Isolated from a Rhesus Macaque. J. Virol. 83: 12738-12750 [Abstract] [Full Text]  
  • Anand, A. R., Prasad, A., Bradley, R. R., Deol, Y. S., Nagaraja, T., Ren, X., Terwilliger, E. F., Ganju, R. K. (2009). HIV-1 gp120-induced migration of dendritic cells is regulated by a novel kinase cascade involving Pyk2, p38 MAP kinase, and LSP1. Blood 114: 3588-3600 [Abstract] [Full Text]  
  • Lu, Y., Song, S. (2009). Distinct immune responses to transgene products from rAAV1 and rAAV8 vectors. Proc. Natl. Acad. Sci. USA 106: 17158-17162 [Abstract] [Full Text]  
  • Lin, J., Zhi, Y., Mays, L., Wilson, J. M. (2007). Vaccines Based on Novel Adeno-Associated Virus Vectors Elicit Aberrant CD8+ T-Cell Responses in Mice. J. Virol. 81: 11840-11849 [Abstract] [Full Text]  
  • Veron, P., Allo, V., Riviere, C., Bernard, J., Douar, A.-M., Masurier, C. (2007). Major Subsets of Human Dendritic Cells Are Efficiently Transduced by Self-Complementary Adeno-Associated Virus Vectors 1 and 2. J. Virol. 81: 5385-5394 [Abstract] [Full Text]  
  • Perreau, M., Mennechet, F., Serratrice, N., Glasgow, J. N., Curiel, D. T., Wodrich, H., Kremer, E. J. (2007). Contrasting Effects of Human, Canine, and Hybrid Adenovirus Vectors on the Phenotypical and Functional Maturation of Human Dendritic Cells: Implications for Clinical Efficacy. J. Virol. 81: 3272-3284 [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»