Intranasal IFN-gamma gene transfer protects BALB/c mice against respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is a major respiratory pathogen in infant s, young children and the elderly and causes severe bronchiolitis and asthm a. In an effort to develop a preventive IFN-gamma therapy against RSV infec tion, an intranasal gene transfer strategy was utilized. Intranasal adminis tration of a plasmid expressing the IFN-gamma cDNA (pIFN-gamma) resulted in the expression of IFN-gamma in murine lungs and decreased RSV replication. The mice administered with pIFN-gamma and then infected with RSV exhibited a significant decrease in broncho-alveolar lavage lymphocyte and neutrophi l counts. A significant reduction in epithelial cell damage, infiltration o f mononuclear cells in the peribronchiolar and perivascular regions, and th ickening of the septa was observed in the lungs of mice treated with pIFN-g amma when compared to controls. These results suggest that intranasal IFN-g amma gene transfer results in decreased RSV replication and pulmonary infla mmation and may be useful against RSV infection. (C) 1999 Elsevier Science Ltd. All rights reserved.