Inhibition of adenovirus-mediated gene transfer by bronchoalveolar lavage fluid

Gene Ther. 1999 Apr;6(4):637-42. doi: 10.1038/


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.

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / immunology
  • Antibodies, Viral / analysis*
  • Bronchoalveolar Lavage Fluid / immunology*
  • Cell Line
  • Gene Expression
  • Gene Transfer Techniques
  • Genetic Vectors / administration & dosage*
  • Humans
  • Immunoglobulin A / analysis
  • Immunoglobulin G / analysis
  • Immunoglobulin M / analysis
  • Immunoglobulins / analysis*
  • Lung Diseases / immunology*


  • Antibodies, Viral
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunoglobulins