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Immune responses to AAV in canine muscle monitored by cellular assays and noninvasive imaging

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Immune responses to AAV in canine muscle monitored by cellular assays and noninvasive imaging. / Wang, Zejing; Storb, Rainer; Lee, Donghoon; Kushmerick, Martin J; Chu, Baocheng; Berger, Carolina; Arnett, Andrea; Allen, James; Chamberlain, Jeffrey S; Riddell, Stanley R; Tapscott, Stephen J.

in: MOL THER, Jahrgang 18, Nr. 3, 03.2010, S. 617-24.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Wang, Z, Storb, R, Lee, D, Kushmerick, MJ, Chu, B, Berger, C, Arnett, A, Allen, J, Chamberlain, JS, Riddell, SR & Tapscott, SJ 2010, 'Immune responses to AAV in canine muscle monitored by cellular assays and noninvasive imaging', MOL THER, Jg. 18, Nr. 3, S. 617-24. https://doi.org/10.1038/mt.2009.294

APA

Wang, Z., Storb, R., Lee, D., Kushmerick, M. J., Chu, B., Berger, C., Arnett, A., Allen, J., Chamberlain, J. S., Riddell, S. R., & Tapscott, S. J. (2010). Immune responses to AAV in canine muscle monitored by cellular assays and noninvasive imaging. MOL THER, 18(3), 617-24. https://doi.org/10.1038/mt.2009.294

Vancouver

Wang Z, Storb R, Lee D, Kushmerick MJ, Chu B, Berger C et al. Immune responses to AAV in canine muscle monitored by cellular assays and noninvasive imaging. MOL THER. 2010 Mär;18(3):617-24. https://doi.org/10.1038/mt.2009.294

Bibtex

@article{2d8bb632adfb441b892b67ae1d26c619,
title = "Immune responses to AAV in canine muscle monitored by cellular assays and noninvasive imaging",
abstract = "We previously demonstrated that direct intramuscular injection of rAAV2 or rAAV6 in wild-type dogs resulted in robust T-cell responses to viral capsid proteins, and others have shown that cellular immunity to adeno-associated virus (AAV) capsid proteins coincided with liver toxicity and elimination of transgene expression in a human trial of hemophilia B. Here, we show that the heparin-binding ability of a given AAV serotype does not determine the induction of T-cell responses following intramuscular injection in dogs, and identify multiple epitopes in the AAV capsid protein that are recognized by T cells elicited by AAV injection. We also demonstrate that noninvasive magnetic resonance imaging (MRI) can accurately detect local inflammatory responses following intramuscular rAAV injection in dogs. These studies suggest that pseudotyping rAAV vectors to remove heparin-binding activity will not be sufficient to abrogate immunogenicity, and validate the utility of enzyme-linked immunosorbent spot (ELISpot) assay and MRI for monitoring immune and inflammatory responses following intramuscular injection of rAAV vectors in preclinical studies in dogs. These assays should be incorporated into future human clinical trials of AAV gene therapy to monitor immune responses.",
keywords = "Animals, Dependovirus/metabolism, Dogs, Enzyme-Linked Immunosorbent Assay/methods, Epitopes/chemistry, Genetic Therapy/methods, Heparan Sulfate Proteoglycans/chemistry, Heparin/metabolism, Immune System/metabolism, Inflammation, Magnetic Resonance Imaging/methods, Microscopy, Fluorescence/methods, Muscles/metabolism, Peptides/chemistry, T-Lymphocytes/immunology",
author = "Zejing Wang and Rainer Storb and Donghoon Lee and Kushmerick, {Martin J} and Baocheng Chu and Carolina Berger and Andrea Arnett and James Allen and Chamberlain, {Jeffrey S} and Riddell, {Stanley R} and Tapscott, {Stephen J}",
year = "2010",
month = mar,
doi = "10.1038/mt.2009.294",
language = "English",
volume = "18",
pages = "617--24",
journal = "MOL THER",
issn = "1525-0016",
publisher = "NATURE PUBLISHING GROUP",
number = "3",

}

RIS

TY - JOUR

T1 - Immune responses to AAV in canine muscle monitored by cellular assays and noninvasive imaging

AU - Wang, Zejing

AU - Storb, Rainer

AU - Lee, Donghoon

AU - Kushmerick, Martin J

AU - Chu, Baocheng

AU - Berger, Carolina

AU - Arnett, Andrea

AU - Allen, James

AU - Chamberlain, Jeffrey S

AU - Riddell, Stanley R

AU - Tapscott, Stephen J

PY - 2010/3

Y1 - 2010/3

N2 - We previously demonstrated that direct intramuscular injection of rAAV2 or rAAV6 in wild-type dogs resulted in robust T-cell responses to viral capsid proteins, and others have shown that cellular immunity to adeno-associated virus (AAV) capsid proteins coincided with liver toxicity and elimination of transgene expression in a human trial of hemophilia B. Here, we show that the heparin-binding ability of a given AAV serotype does not determine the induction of T-cell responses following intramuscular injection in dogs, and identify multiple epitopes in the AAV capsid protein that are recognized by T cells elicited by AAV injection. We also demonstrate that noninvasive magnetic resonance imaging (MRI) can accurately detect local inflammatory responses following intramuscular rAAV injection in dogs. These studies suggest that pseudotyping rAAV vectors to remove heparin-binding activity will not be sufficient to abrogate immunogenicity, and validate the utility of enzyme-linked immunosorbent spot (ELISpot) assay and MRI for monitoring immune and inflammatory responses following intramuscular injection of rAAV vectors in preclinical studies in dogs. These assays should be incorporated into future human clinical trials of AAV gene therapy to monitor immune responses.

AB - We previously demonstrated that direct intramuscular injection of rAAV2 or rAAV6 in wild-type dogs resulted in robust T-cell responses to viral capsid proteins, and others have shown that cellular immunity to adeno-associated virus (AAV) capsid proteins coincided with liver toxicity and elimination of transgene expression in a human trial of hemophilia B. Here, we show that the heparin-binding ability of a given AAV serotype does not determine the induction of T-cell responses following intramuscular injection in dogs, and identify multiple epitopes in the AAV capsid protein that are recognized by T cells elicited by AAV injection. We also demonstrate that noninvasive magnetic resonance imaging (MRI) can accurately detect local inflammatory responses following intramuscular rAAV injection in dogs. These studies suggest that pseudotyping rAAV vectors to remove heparin-binding activity will not be sufficient to abrogate immunogenicity, and validate the utility of enzyme-linked immunosorbent spot (ELISpot) assay and MRI for monitoring immune and inflammatory responses following intramuscular injection of rAAV vectors in preclinical studies in dogs. These assays should be incorporated into future human clinical trials of AAV gene therapy to monitor immune responses.

KW - Animals

KW - Dependovirus/metabolism

KW - Dogs

KW - Enzyme-Linked Immunosorbent Assay/methods

KW - Epitopes/chemistry

KW - Genetic Therapy/methods

KW - Heparan Sulfate Proteoglycans/chemistry

KW - Heparin/metabolism

KW - Immune System/metabolism

KW - Inflammation

KW - Magnetic Resonance Imaging/methods

KW - Microscopy, Fluorescence/methods

KW - Muscles/metabolism

KW - Peptides/chemistry

KW - T-Lymphocytes/immunology

U2 - 10.1038/mt.2009.294

DO - 10.1038/mt.2009.294

M3 - SCORING: Journal article

C2 - 20040912

VL - 18

SP - 617

EP - 624

JO - MOL THER

JF - MOL THER

SN - 1525-0016

IS - 3

ER -