NDLI: Humoral and cellular capsid-specific immune responses to adeno-associated virus type 1 in randomized healthy donors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Veron, Philippe Masurier, Carole Monteilhet, Virginie Moullier, Philippe Boutin, Sylvie Martin, Samia Leborgne, Christian
Description	Country affiliation: France Author Affiliation: Veron P ( Laboratoire d'Immunologie, Genethon, 91002 Evry Cedex, France.)
Abstract	A major impediment to the use of adeno-associated virus (AAV)-mediated gene delivery to muscle in clinical applications is the pre-existing immune responses against the vector. Pre-existing humoral response to different AAV serotypes is now well documented. In contrast, cellular responses to AAV capsid have not been analyzed in a systematic manner, despite the risk of T cell reactivation upon gene transfer. AAV1 has been widely used in humans to target muscle. In this study, we analyzed PBMCs and sera of healthy donors for the presence of AAV1 capsid-specific T cell responses and AAV1 neutralizing factors. Approximately 30% of donors presented AAV1 capsid-specific T cells, mainly effector memory CD8(+) cells. IFN-Î³-producing cells were also observed among effector memory CD4(+) cells for two of these donors. Moreover, to our knowledge, this study shows for the first time on a large cohort that there was no correlation between AAV1-specific T cell and humoral responses. Indeed, most donors presenting specific Ig and neutralizing factors were negative for cellular response (and vice versa). These new data raise the question of prescreening patients not only for the humoral response, but also for the cellular response. Clearly, a better understanding of the natural immunology of AAV serotypes will allow us to improve AAV gene therapy and make it an efficient treatment for genetic disease.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	12
Volume Number	188
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Capsid Proteins Immunology Dependovirus Immunity, Cellular Immunity, Humoral Immunologic Memory Enzyme-linked Immunosorbent Assay Flow Cytometry Genetic Therapy Genetic Vectors Random Allocation T-lymphocytes Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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