Brief Communication abstract


Nature Medicine 13, 419 - 422 (2007)
Published online: 18 March 2007 | doi:10.1038/nm1549

CD8+ T-cell responses to adeno-associated virus capsid in humans

Federico Mingozzi1,11, Marcela V Maus1,2,11, Daniel J Hui1,11, Denise E Sabatino1, Samuel L Murphy1, John E J Rasko3,4, Margaret V Ragni5, Catherine S Manno1,6, Jurg Sommer7,10, Haiyan Jiang7,10, Glenn F Pierce7,10, Hildegund C J Ertl8 & Katherine A High1,6,9

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Hepatic adeno-associated virus (AAV)-serotype 2 mediatedgene transfer results in transgene product expression that is sustained in experimental animals but not in human subjects. We hypothesize that this is caused by rejection of transduced hepatocytes by AAV capsid–specific memory CD8+ T cells reactivated by AAV vectors. Here we show that healthy subjects carry AAV capsid–specific CD8+ T cells and that AAV-mediated gene transfer results in their expansion. No such expansion occurs in mice after AAV-mediated gene transfer. In addition, we show that AAV-2 induced human T cells proliferate upon exposure to alternate AAV serotypes, indicating that other serotypes are unlikely to evade capsid-specific immune responses.

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  1. The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.
  2. Hospital of the University of Pennsylvania, Department of Medicine, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
  3. Gene and Stem Cell Therapy Program, Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney, New South Wales, Australia.
  4. Cell & Molecular Therapies, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
  5. University of Pittsburgh Medical Center, Hemophilia Center of Western Pennsylvania, 3636 Boulevard of the Allies, Pittsburgh, Pennsylvania 15213, USA.
  6. University of Pennsylvania School of Medicine, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.
  7. Avigen, Inc., 1301 Harbor Bay Parkway, Alameda, California 94502, USA.
  8. The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA.
  9. Howard Hughes Medical Institute, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.
  10. Present address: Bayer HealthCare LLC, 800 Dwight Way, Berkeley, California 94710, USA.
  11. These authors contributed equally to this work.

Correspondence to: Katherine A High1,6,9 e-mail: high@email.chop.edu



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