title: Inhibition of adenovirus-mediated gene transfer by bronchoalveolar lavage fluid.
abstract: Human and animal trials with recombinant adenovirus have been discouraging, since the level of recombinant gene expression was low. Nonspecific and specific immune response mediated by, for example, macrophages, T cells and immunoglobulins may prevent infection or cause death of infected cells. We analyzed the effect of bronchoalveolar lavage fluid (BAL) on the efficiency of adenoviral infection in vitro. A total of 26 BAL samples of randomly selected patients was examined. Adenovirus-mediated gene transfer was quantified using AdCMV. Null, a recombinant adenovirus, in a modified titer assay based on immunocytochemical detection of infected 293 cells. In addition, the concentration of anti-adenovirus-type 5 IgA, IgG and IgM antibodies in BAL was determined by ELISA. 53.8% of the BAL samples (14 out of 26) reduced adenoviral infectivity by at least 50% (factor of inhibition > or = 2). All BAL samples effecting, a reduction in adenoviral infectivity contained detectable amounts of anti-adenovirus-type 5-IgA antibodies. However, the correlation between the concentration of IgA antibody and the strength of inhibition was weak (r = 0.336). Even high levels of anti-adenovirus-type 5-IgM, IgG or IgA antibodies did not influence adenoviral infectivity consistently. This observation indicates that BAL contains (a) anti-adenovirus-type 5 antibodies which are not directed against adenoviral epitopes responsible for the viral adherence and uptake process; and/or (b) inhibitors of viral infectivity different from antibodies.
authors.affiliation: First Department of Internal Medicine, Christian-Albrechts-University of Kiel, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Bastian
authors.forename: B
authors.initials: B
authors.lastname: Bewig
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000914:Antibodies, Viral / Q000032:analysis*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D002460:Cell Line; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007136:Immunoglobulins / Q000032:analysis*; D008171:Lung Diseases / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins