Antigen-Specific Tolerance of Human alpha(1)-Antitrypsin Induced by Helper-Dependent Adenovirus.

Antigen-Specific Tolerance of Human alpha(1)-Antitrypsin Induced by Helper-Dependent Adenovirus. Research Abstract Details 

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Antigen-Specific Tolerance of Human alpha(1)-Antitrypsin Induced by Helper-Dependent Adenovirus. Abstract Text:

V Cerullo,W McCormack,M Seiler,V Mane,R Cela,C Clarke,J R Rodgers,B Lee,V Cerullo,W McCormack,M Seiler,V Mane,R Cela,C Clarke,J R Rodgers,B Lee,V Cerullo,W McCormack,M Seiler,V Mane,R Cela,C Clarke,J R Rodgers,B Lee,

As efficient and less toxic virus-derived gene therapy vectors are developed, a pressing problem is to avoid immune response to the therapeutic gene product. Secreted therapeutic proteins potentially represent a special problem, as they are readily available to professional antigen-presenting cells throughout the body. Some studies suggest that immunity to serum proteins can be avoided in some mouse strains by using tissue-specific promoters. Here we show that expression of human alpha(1)-antitrypsin (AAT) was nonimmunogenic in the immune-responsive strain C3H/HeJ, when expressed from helper-dependent (HD) vectors using ubiquitous as well as tissue-specific promoters. Coadministration of less immunogenic HD vectors with an immunogenic first-generation vector failed to immunize, suggesting immune suppression rather than immune stealth. Indeed, mice primed with HD vectors were tolerant to immune challenge with hAAT emulsified in complete Freund's adjuvant. Such animals developed high-titer antibodies to coemulsified human serum albumin, showing that tolerance was antigen specific. AAT-specific T cell responses were depressed in tolerized animals, suggesting that tolerance affects both T and B cells. These results are consistent with models of high-dose tolerance of B cells and certain other suppressive mechanisms, and suggest that a high level of expression from HD vectors can be sufficient to induce specific immune tolerance to serum proteins.

Antigen-Specific Tolerance of Human alpha(1)-Antitrypsin Induced by Helper-Dependent Adenovirus. Publishing Authors By Initials

V Cerullo,W McCormack,M Seiler,V Mane,R Cela,C Clarke,JR Rodgers,B Lee,V Cerullo,W McCormack,M Seiler,V Mane,R Cela,C Clarke,JR Rodgers,B Lee,V Cerullo,W McCormack,M Seiler,V Mane,R Cela,C Clarke,JR Rodgers,B Lee,

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Antigen-Specific Tolerance of Human alpha(1)-Antitrypsin Induced by Helper-Dependent Adenovirus. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Human gene therapy

VOLUME: 18

Page Numbers: 1215-24

Journal Abbreviation: Hum. Gene Ther.

ISSN: 1043-0342

DAY: 17

MONTH: Dec

YEAR: 2007

Antigen-Specific Tolerance of Human alpha(1)-Antitrypsin Induced by Helper-Dependent Adenovirus. Information

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LANGUAGE: eng

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AFFILIATION: Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

Country: United States

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MEDLINETA: Hum Gene Ther

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