Inhibition of adenovirus-mediated gene transfer by bronchoalveolar lavage fluid
- 1 April 1999
- journal article
- Published by Springer Nature in Gene Therapy
- Vol. 6 (4) , 637-642
- https://doi.org/10.1038/sj.gt.3300854
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.Keywords
This publication has 24 references indexed in Scilit:
- Innate Immune Mechanisms Dominate Elimination of Adenoviral Vectors FollowingIn VivoAdministrationHuman Gene Therapy, 1997
- Upregulation of class I major histocompatibility complex antigens by interferon gamma is necessary for T-cell-mediated elimination of recombinant adenovirus-infected hepatocytes in vivo.Proceedings of the National Academy of Sciences, 1995
- Transfer of the CFTR Gene to the Lung of Nonhuman Primates with E1-Deleted, E2a-Defective Recombinant Adenoviruses: A Preclinical Toxicology StudyHuman Gene Therapy, 1995
- Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosisNature Genetics, 1994
- Inactivation of E2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosisNature Genetics, 1994
- Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy.Proceedings of the National Academy of Sciences, 1994
- In vivo hepatic gene therapy: complete albeit transient correction of factor IX deficiency in hemophilia B dogs.Proceedings of the National Academy of Sciences, 1994
- Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosisPublished by Elsevier ,1993
- Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery.Journal of Clinical Investigation, 1993
- In vivo transfer of the human cystic fibrosis transmembrane conductance regulator gene to the airway epitheliumCell, 1992