Human Immune Responses to Adeno-Associated Virus (AAV) Vectors

Recombinant adeno-associated virus (rAAV) vectors are one of the most promising gene delivery tools. Several features make rAAV vectors an ideal platform for gene transfer. However, the high homology with the parental wild-type virus, which often infects humans, poses limitations in terms of immune...

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Published in:Frontiers in immunology Vol. 11; p. 670
Main Authors: Ronzitti, Giuseppe, Gross, David-Alexandre, Mingozzi, Federico
Format: Journal Article
Language:English
Published: Switzerland Frontiers 17.04.2020
Frontiers Media S.A
Subjects:
AAV vectors
Adenoviridae - genetics
B cells
B-Lymphocytes - immunology
clinical trials
Clinical Trials as Topic
gene therapy
Genetic Therapy - trends
Genetic Vectors - genetics
Humans
Immunity
Immunology
Life Sciences
Lymphocyte Activation
T cells
T-Lymphocytes - immunology
gene therapy
AAV vectors
clinical trials
B cells
T cells
AAV vectors, gene therapy, T cells, B cells, clinical trials
ISSN:1664-3224, 1664-3224
Online Access:Get full text
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Summary:Recombinant adeno-associated virus (rAAV) vectors are one of the most promising gene delivery tools. Several features make rAAV vectors an ideal platform for gene transfer. However, the high homology with the parental wild-type virus, which often infects humans, poses limitations in terms of immune responses associated with this vector platform. Both humoral and cell-mediated immunity to wild-type AAV have been documented in healthy donors, and, at least in the case of anti-AAV antibodies, have been shown to have a potentially high impact on the outcome of gene transfer. While several factors can contribute to the overall immunogenicity of rAAV vectors, vector design and the total vector dose appear to be responsible of immune-mediated toxicities. While preclinical models have been less than ideal in predicting the outcome of gene transfer in humans, the current preclinical body of evidence clearly demonstrates that rAAV vectors can trigger both innate and adaptive immune responses. Data gathered from clinical trials offers key learnings on the immunogenicity of AAV vectors, highlighting challenges as well as the potential strategies that could help unlock the full therapeutic potential of gene transfer.
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Edited by: Moriya Tsuji, Columbia University Irving Medical Center, United States
This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology
Reviewed by: Nathalie Clement, University of Florida, United States; Chengwen Li, The University of North Carolina at Chapel Hill, United States
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2020.00670