Gene therapy with a replication defective recombinant adenovirus has emerged as a viable strategy for correcting the genetic defect in cystic fibrosis (CF). The prevalence of adenovirus (Ad) specific antibodies in serum may influence the infectivity of the adenovirus vector. In children, Ad infections are common with types 1 through 7 accounting for approximately 85% of infections. In this study, we determined the prevalence of neutralizing antibodies to Ad types 1 through 7 in children with CF and in many of their mothers. 78 CF children mean age 3.3 years (0.5 to 8.7 yrs) were followed for a mean of 13.1 months (0.03 to 19.1 mo). 47 mothers of CF children were also followed. Blood specimens were obtained every 3 to 6 months during the study and were tested for Ad type specific neutralizing antibodies with a microneutralization assay. Subjects with Ad type specific neutralizing antibody titers ≥ 3.5 log2 were considered to have been infected with that Ad type. Illustrated in the table is the percent of subjects with Ad type specific neutralizing antibody titers ≥ 3.5 log2. As expected, CF children had lower seroprevalence to the common adenoviruses compared to their mothers. Seroprevalence data to Ad types 1, 2, 4, 5, 6, and 7 were consistent with the age distribution of infection with adenoviruses. However we observed a very high percent of CF children with Ad 3 specific antibody. Our observations suggest that the majority of CF children will not contain antibodies that will interfere with the sequential administration of the normal CF gene packaged in different types of Ad vectors.

Table 1
Full size table