ADENOVIRUS INFECTION IN CYSTIC-FIBROSIS PATIENTS - IMPLICATIONS FOR THE USE OF ADENOVIRAL VECTORS FOR GENE-TRANSFER

Clinical trials using replication-deficient adenovirus as vectors for gene transfer into the airways of cystic fibrosis (CF) patients are in progress, However, little is known about the prevalence of wild-type adenovirus infections in patients with cystic fibrosis and their effec t on lung function, To answer these questions, serum IgG and IgM antib ody titers against adenovirus type 5 were prospectively measured by an indirect immunofluorescence assay in 199 CF outpatients and in a cont rol group of 45 healthy children and young adults, In addition, we per formed pulmonary function tests when the patients were in stable clini cal condition, IgM antibodies against adenovirus were present in 104 o f the 199 cystic fibrosis patients (52.3%), IgG antibodies against ade novirus were detected in 192 of the 199 cystic fibrosis patients (96.5 %), and were significantly higher in cystic fibrosis patients older th an 7 years than in younger patients and in age matched controls, IgG a ntibody titers measured a second time 11.8 months later in 143 of the 199 patients had increased in 48 (33.6%) patients, In 27 of these 48 p atients, who had at least a 2-fold increase in antibody titer, FVC and FEV(1) decreased by 9.8% (p<0.05) and 8.3% (p=0,05), respectively, ov er 45 months, In a comparison group matched for age, sex, and chronic Pseudomonas aeruginosa infection but no increase in antibody titers, F VC and FEV(1) were unchanged. The results indicate that wild-type aden ovirus infections are prevalent fi cystic fibrosis patients and that w ild-type adenovirus infections in cystic fibrosis patients seem to be associated with deterioration in lung function, These observations may have important implications for efficacy and safety considerations wh en using adenoviral vectors for gene therapy.