Incidence and prevalence of neutralizing antibodies to the common adenoviruses in children with cystic fibrosis: implication for gene therapy with adenovirus vectors

OBJECTIVE: Defining the infection rate and prevalence of the common adenoviruses (Ads) in cystic fibrosis (CF) children may aid in formulation of strategies for gene therapy with Ad vectors. We undertook this study to determine the incidence and prevalence of infection with the common Ads in children with CF. METHODOLOGY: Thirty newly diagnosed CF children mean age 1.1 years (Group 1), 48 CF children mean age 4.6 years (Group 2), and 47 mothers of CF children (Group 3) were followed for a mean of 13 months. Group 4 consisted of 33 adult volunteers seen once. Throat and stool specimens for virus culture, and blood samples were obtained every 3 months from CF children in Group 1. Blood samples from CF children (Group 2) and their mothers (Group 3) were obtained every 6 months, and once from adults in Group 4. Neutralizing antibody to Ad serotypes 1 through 7 (Ad 1 to Ad 7) was evaluated with a microneutralization assay. RESULTS: Five (16.7%) CF children in Group 1 were culture-positive for an Ad; 4 of these CF children developed a fourfold or greater rise in antibody titer. Ad 3 infection occurred frequently based on serology; seronegative (< 3.5 log 2) CF children had a higher infection rate compared with seropositive CF children (7/11 vs 1/34). The prevalence of neutralizing antibodies in CF children in order of decreasing frequency was 91.1% to Ad 3, 37.5% to Ad 2, 27.1% to Ad 1, 26.1% to Ad 7, 16.7% to Ad 5, 8.5% to Ad 4, and 2.0% to Ad 6. The neutralizing antibody titers in seropositive CF children were comparable to those in adults except to Ad 3, which was significantly greater in mothers of CF children. CONCLUSIONS: CF children had a normal antibody response after Ad infection, preexisting antibody may protect against reinfection and antibody prevalence was low to the common Ads.