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 Halbert, C. L.
Right arrow Articles by Miller, A. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Halbert, C. L.
Right arrow Articles by Miller, A. D.

 Previous Article  |  Next Article 

Journal of Virology, December 1998, p. 9795-9805, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Successful Readministration of Adeno-Associated Virus Vectors to the Mouse Lung Requires Transient Immunosuppression during the Initial Exposure

Christine L. Halbert,1 Thomas A. Standaert,2 Christopher B. Wilson,3 and A. Dusty Miller1,4,*

Fred Hutchinson Cancer Research Center, Seattle, Washington 98109,1 and Departments of Pediatrics,2 Medicine,3 and Pathology,4 University of Washington, Seattle, Washington 98195

Received 26 March 1998/Accepted 8 September 1998

The airway is an important target for gene transfer to treat cystic fibrosis and other diseases that affect the lung. We previously found that marker gene expression did not persist in the bronchial epithelium following adeno-associated virus (AAV) vector administration to the rabbit lung. In an attempt to promote continued expression, we tested repeat vector administration, but no additional transduction was observed, and the block to transduction correlated with the appearance of neutralizing antibodies to the viral capsid. Here we show that mice exhibit a similar response but that treatment with anti-CD40 ligand antibody (MR1) and a soluble CTLA4-immunoglobulin fusion protein (CTLA4Ig) at the time of primary AAV vector exposure allowed successful repeat transduction and prevented production of neutralizing antibodies. We also tested the possibility that an immune response caused the loss of marker-positive cells in the epithelial population in rabbits by evaluating AAV vector expression in immunocompetent and immunodeficient mice. In contrast to results in rabbits, marker protein expression persisted in the lung in both groups of mice. AAV vector transduction occurred in alveolar cells, airway epithelial cells, and smooth muscle cells, and vector expression persisted for at least 8 months. Although data on persistence of AAV vector expression in the human lung are not available, it is likely that repeat transduction will be necessary either due to loss of expression or to the need for repeat administration to deliver effective amounts of AAV vectors. Results presented here indicate that transient immunosuppression will allow such repeat vector treatment of the lung.

* Corresponding author. Mailing address: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. North, Room C2-023, Seattle, WA 98109-1024. Phone: (206) 667-2890. Fax: (206) 667-6523. E-mail: dmiller{at}fhcrc.org.

Journal of Virology, December 1998, p. 9795-9805, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Daya, S., Berns, K. I. (2008). Gene Therapy Using Adeno-Associated Virus Vectors. Clin. Microbiol. Rev. 21: 583-593 [Abstract] [Full Text]  
  • Sumner-Jones, S. G., Gill, D. R., Hyde, S. C. (2007). Lack of Repeat Transduction by Recombinant Adeno-Associated Virus Type 5/5 Vectors in the Mouse Airway. J. Virol. 81: 12360-12367 [Abstract] [Full Text]  
  • Kuck, D., Lau, T., Leuchs, B., Kern, A., Muller, M., Gissmann, L., Kleinschmidt, J. A. (2006). Intranasal Vaccination with Recombinant Adeno-Associated Virus Type 5 against Human Papillomavirus Type 16 L1. J. Virol. 80: 2621-2630 [Abstract] [Full Text]  
  • Alton, E. W. F. W., on behalf of the United Kingdom Cystic Fibrosis Ge, (2004). Use of Nonviral Vectors for Cystic Fibrosis Gene Therapy. Proc Am Thorac Soc 1: 296-301 [Abstract] [Full Text]  
  • Sandalon, Z., Bruckheimer, E. M., Lustig, K. H., Rogers, L. C., Peluso, R. W., Burstein, H. (2004). Secretion of a TNFR:Fc Fusion Protein following Pulmonary Administration of Pseudotyped Adeno-Associated Virus Vectors. J. Virol. 78: 12355-12365 [Abstract] [Full Text]  
  • Peden, C. S., Burger, C., Muzyczka, N., Mandel, R. J. (2004). Circulating Anti-Wild-Type Adeno-Associated Virus Type 2 (AAV2) Antibodies Inhibit Recombinant AAV2 (rAAV2)-Mediated, but Not rAAV5-Mediated, Gene Transfer in the Brain. J. Virol. 78: 6344-6359 [Abstract] [Full Text]  
  • Liu, S.-L., Halbert, C. L., Miller, A. D. (2004). Jaagsiekte Sheep Retrovirus Envelope Efficiently Pseudotypes Human Immunodeficiency Virus Type 1-Based Lentiviral Vectors. J. Virol. 78: 2642-2647 [Abstract] [Full Text]  
  • Mastakov, M. Y., Baer, K., Symes, C. W., Leichtlein, C. B., Kotin, R. M., During, M. J. (2002). Immunological Aspects of Recombinant Adeno-Associated Virus Delivery to the Mammalian Brain. J. Virol. 76: 8446-8454 [Abstract] [Full Text]  
  • Coil, D. A., Strickler, J. H., Rai, S. K., Miller, A. D. (2001). Jaagsiekte Sheep Retrovirus Env Protein Stabilizes Retrovirus Vectors against Inactivation by Lung Surfactant, Centrifugation, and Freeze-Thaw Cycling. J. Virol. 75: 8864-8867 [Abstract] [Full Text]  
  • KOLB, M., INMAN, M., MARGETTS, P. J., GALT, T., GAULDIE, J. (2001). Budesonide Enhances Repeated Gene Transfer and Expression in the Lung with Adenoviral Vectors. Am. J. Respir. Crit. Care Med. 164: 866-872 [Abstract] [Full Text]  
  • Halbert, C. L., Allen, J. M., Miller, A. D. (2001). Adeno-Associated Virus Type 6 (AAV6) Vectors Mediate Efficient Transduction of Airway Epithelial Cells in Mouse Lungs Compared to That of AAV2 Vectors. J. Virol. 75: 6615-6624 [Abstract] [Full Text]  
  • RICHTER, M., IWATA, A., NYHUIS, J., NITTA, Y., MILLER, A. D., HALBERT, C. L., ALLEN, M. D. (2000). Adeno-associated virus vector transduction of vascular smooth muscle cells in vivo. Physiol. Genomics 2: 117-127 [Abstract] [Full Text]  
  • Zabner, J., Seiler, M., Walters, R., Kotin, R. M., Fulgeras, W., Davidson, B. L., Chiorini, J. A. (2000). Adeno-Associated Virus Type 5 (AAV5) but Not AAV2 Binds to the Apical Surfaces of Airway Epithelia and Facilitates Gene Transfer. J. Virol. 74: 3852-3858 [Abstract] [Full Text]  
  • Chirmule, N., Xiao, W., Truneh, A., Schnell, M. A., Hughes, J. V., Zoltick, P., Wilson, J. M. (2000). Humoral Immunity to Adeno-Associated Virus Type 2 Vectors following Administration to Murine and Nonhuman Primate Muscle. J. Virol. 74: 2420-2425 [Abstract] [Full Text]  
  • Moskalenko, M., Chen, L., van Roey, M., Donahue, B. A., Snyder, R. O., Mcarthur, J. G., Patel, S. D. (2000). Epitope Mapping of Human Anti-Adeno-Associated Virus Type 2 Neutralizing Antibodies: Implications for Gene Therapy and Virus Structure. J. Virol. 74: 1761-1766 [Abstract] [Full Text]  
  • Halbert, C. L., Rutledge, E. A., Allen, J. M., Russell, D. W., Miller, A. D. (2000). Repeat Transduction in the Mouse Lung by Using Adeno-Associated Virus Vectors with Different Serotypes. J. Virol. 74: 1524-1532 [Abstract] [Full Text]  
  • Walters, R. W., Duan, D., Engelhardt, J. F., Welsh, M. J. (2000). Incorporation of Adeno-Associated Virus in a Calcium Phosphate Coprecipitate Improves Gene Transfer to Airway Epithelia In Vitro and In Vivo. J. Virol. 74: 535-540 [Abstract] [Full Text]  
  • Beck, S. E., Jones, L. A., Chesnut, K., Walsh, S. M., Reynolds, T. C., Carter, B. J., Askin, F. B., Flotte, T. R., Guggino, W. B. (1999). Repeated Delivery of Adeno-Associated Virus Vectors to the Rabbit Airway. J. Virol. 73: 9446-9455 [Abstract] [Full Text]  
  • Xiao, W., Chirmule, N., Berta, S. C., McCullough, B., Gao, G., Wilson, J. M. (1999). Gene Therapy Vectors Based on Adeno-Associated Virus Type 1. J. Virol. 73: 3994-4003 [Abstract] [Full Text]  
  • Walters, R. W., Yi, S. M. P., Keshavjee, S., Brown, K. E., Welsh, M. J., Chiorini, J. A., Zabner, J. (2001). Binding of Adeno-associated Virus Type 5 to 2,3-Linked Sialic Acid Is Required for Gene Transfer. J. Biol. Chem. 276: 20610-20616 [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»