Inhibition of adenovirus-mediated gene transfer by bronchoalveolar lavage fluid

Human and animal trials with recombinant adenovirus have been discouraging, since the level of recombinant gene expression was low Nonspecific and spe cific immune response mediated by, for example, macrophages, T cells and im munoglobulins may prevent infection or cause death of infected cells. We an alyzed the effect of bronchoalveolar lavage fluid (BAL) on the efficiency o f adenoviral infection in vitro. A fetal of 26 BAL samples of randomly sele cted patients was examined. Adenovirus-mediated gene transfer was quantifie d using AdCMV.Null, a recombinant adenovirus, in a modified titer assay bas ed 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 ad enoviral infectivity by at least 50% (factor of inhibition greater than or equal to 2). An BAL samples effecting a reduction in adenoviral infectivity contained detectable amounts of anti-adenovirus-type 5-IgA antibodies. How ever, the correlation between the concentration of IgA antibody and the str ength of inhibition was weak (r= 0.336). Even high levels of anti-adenoviru s-type 5-IgM, IgG or IgA antibodies did not influence adenoviral infectivit y consistently. This observation indicates that BAL contains (a) anfi-adeno virus-type 5 antibodies which are not directed against adenoviral epitopes responsible for the viral adherence and uptake process; and/or (b) inhibito rs of viral infectivity different from antibodies.