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

• Published in: Blood Vol. 101; no. 7; pp. 2551 - 2556
• Main Authors: De Geest, Bart R., Van Linthout, Sophie A., Collen, Désiré
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.04.2003; The Americain Society of Hematology
• Subjects: Adenoviridae - genetics; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antibodies, Heterophile - blood; Antibody Formation; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigens, Heterophile - blood; Antigens, Heterophile - genetics; Antigens, Heterophile - immunology; Apolipoprotein A-I - blood; Apolipoprotein A-I - genetics; Apolipoprotein A-I - immunology; Applied cell therapy and gene therapy; Biological and medical sciences; Gene Transfer Techniques - standards; Genetic Vectors; Humans; Immune Tolerance; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Transgenic; Promoter Regions, Genetic; RNA, Messenger - analysis; Spleen - cytology; Spleen - immunology; Spleen - metabolism; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Animal model; Antigen presentation; Adenoviridae; Immune response; Rodentia; Gene expression; Transgene; Genetic transfer; Virus; Apolipoprotein A; Vertebrata; Mammalia; Mouse; Antigen presenting cell; Animal; Gene therapy; Humoral immunity
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-07-2146

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 activeCMVpromoter but induces no immune response when driven by the hepatocyte-specific 256–base pairapo A-Ipromoter. 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-specificapo C-IIor 1.5-kilobase (kb) humanα1-antitrypsinpromoter, but antibodies were induced after transfer with vectors driven by the ubiquitously activeU1bpromoter and the murineMHCII Eβpromoter. A strict correlation was observed between antigen expression in the spleen and the occurrence of an immune response. Coinjection of the 1.5-kb humanα1-antitrypsinand the murineMHCII Eβpromoter–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 theMHCII Eβpromoter–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.