Author: ["Federico Mingozzi","Marcela V Maus","Daniel J Hui","Denise E Sabatino","Samuel L Murphy","John E J Rasko","Margaret V Ragni","Catherine S Manno","Jurg Sommer","Haiyan Jiang","Glenn F Pierce","Hildegund C J Ertl","Katherine A High"]
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Abstract
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.
Cite this article
Mingozzi, F., Maus, M., Hui, D. et al. CD8+ T-cell responses to adeno-associated virus capsid in humans. Nat Med 13, 419–422 (2007). https://doi.org/10.1038/nm1549