ORCID Profile
0000-0001-7533-8717
Current Organisation
Autonomous University of Barcelona
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Publisher: Frontiers Media SA
Date: 22-05-2019
Publisher: MyJove Corporation
Date: 27-09-2018
DOI: 10.3791/58366
Publisher: The University of Queensland; Fisheries Research and Development Corporation
Date: 02-2023
DOI: 10.14264/1444C70
Publisher: Springer Science and Business Media LLC
Date: 20-11-2015
DOI: 10.1038/GT.2014.103
Abstract: Simian adeno-associated virus (AAV) serotype rh.10 is a promising gene therapy tool, achieving safe, sustained transgene expression in the nervous system, lung, liver and heart in animal models. To date, preexisting immunity in humans has not been confirmed, though exposure is unexpected. We compared the humoral immune response with serotypes AAVrh.10 and AAV9 in mice, and AAVrh.10, AAV9 and AAV2 in 100 healthy humans. Mice, injected-intravenously, raised significantly more anti-AAV9 than anti-AAVrh.10 IgG (immunoglobulins), and sera demonstrated greater neutralizing capacity, correspondingly. Antibody cross-binding studies in mice showed negligible cross-recognition between AAVrh.10, AAV9 and AAV2. In humans, IgG prevalence against the most common human serotype, AAV2, was 72% AAV9, 47% and AAVrh.10, a surprising, 59%. Yet, neutralizing-antibody seroprevalences were 71% for AAV2, 18% for AAV9 and 21% for AAVrh.10. Thus, most anti-AAV9 and anti-AAVrh.10 IgG were nonneutralizing. Indeed, sera generally neutralized AAV2 more strongly than AAVrh.10. Further, all s les neutralizing AAVrh.10 or AAV9 also neutralized AAV2, suggesting antibody cross-recognition. This contrasts with the results in mice, and highlights the complexity of tailoring gene therapy to minimize the immune response in humans, when multiple-mixed infections during a lifetime evoke a broad repertoire of preexisting antibodies capable of cross reacting with non-human serotypes.
Publisher: Elsevier BV
Date: 02-2022
Publisher: Elsevier BV
Date: 06-2021
Publisher: Frontiers Media SA
Date: 18-07-2018
Publisher: Elsevier BV
Date: 04-2020
Publisher: Elsevier BV
Date: 08-2019
No related grants have been discovered for Rosemary Thwaite.