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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-07-2146.

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Blood, 1 April 2003, Vol. 101, No. 7, pp. 2551-2556

GENE THERAPY

Humoral immune response in mice against a circulating antigen induced by adenoviral transfer is strictly dependent on expression in antigen-presenting cells

Bart R. De Geest, Sophie A. Van Linthout, and Désiré Collen

From the Center for Molecular and Vascular Biology, Department for Molecular and Cardiovascular Research, Leuven, Belgium.

Adenoviral transfer of human apo A-I in Balb/c mice induces a strong humoral immune response against the transgene product when expression is driven from the ubiquitously active CMV promoter but induces no immune response when driven by the hepatocyte-specific 256-base pair apo A-I promoter. Here the hypothesis was tested, which is that the humoral immune response against the circulating transgene product correlates with its expression in antigen-presenting cells. No humoral immune response was observed after adenoviral transfer of vectors with human apo A-I expression driven by the hepatocyte-specific apo C-II or 1.5-kilobase (kb) human alpha 1-antitrypsin promoter, but antibodies were induced after transfer with vectors driven by the ubiquitously active U1b promoter and the murine MHCII Ebeta promoter. A strict correlation was observed between antigen expression in the spleen and the occurrence of an immune response. Coinjection of the 1.5-kb human alpha 1-antitrypsin and the murine MHCII Ebeta promoter-driven vectors resulted in a very short-lived humoral immune response against human apo A-I, suggesting that the time course of human apo A-I expression is a critical determinant of the development of tolerance for human apo A-I. High titers of antibodies against human apo A-I after subcutaneous gene transfer with the MHCII Ebeta promoter-driven vector underscore the potential of this promoter for vaccination purposes. In conclusion, humoral immune response in mice against a circulating antigen induced by adenoviral transfer is strictly dependent on expression in antigen-presenting cells.

© 2003 by The American Society of Hematology.
 

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