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 ad enoviruses (Ads) in cystic fibrosis (Cm children may aid in formulatio n of strategies for gene therapy with Ad vectors. We undertook this st udy to determine the incidence and prevalence of infection with the co mmon Ads in children with CF. Methodology. Thirty newly diagnosed CF c hildren mean age 1.1 years (Group 1), 48 CF children mean age 4.6 year s (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 on ce. Throat and stool specimens for virus culture, and blood samples we re obtained every 3 months from CF children in Group 1. Blood samples from CF children (Group 2) and their mothers (Group 3) were obtained e very 6 months, and once from adults in Group 4. Neutralizing antibody to Ad serotypes 1 through 7 (Ad I to Ad 7) was evaluated with a micron eutralization assay. Results. Five (16.7%) CF children in Group 1 were culture-positive for an Ad; 4 of these CF children developed a fourfo ld or greater rise in antibody titer. Ad 3 infection occurred frequent ly based on serology; seronegative (<3.5 log 2) CF children had a high er infection rate compared with seropositive CF children (7/11 vs 1/34 ). The prevalence of neutralizing antibodies in CF children in order o f 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 neu tralizing 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.