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 effect on lung function. To answer these questions, serum IgG and IgM antibody titers against adenovirus type 5 were prospectively measured by an indirect immunofluorescence assay in 199 CF outpatients and in a control group of 45 healthy children and young adults. In addition, we performed pulmonary function tests when the patients were in stable clinical condition. IgM antibodies against adenovirus were present in 104 of the 199 cystic fibrosis patients (52.3%). IgG antibodies against adenovirus were detected in 192 of the 199 cystic fibrosis patients (96.5%), and were significantly higher in cystic fibrosis patients older than 7 years than in younger patients and in age matched controls. IgG antibody 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 patients, who had at least a 2-fold increase in antibody titer, FVC and FEV1 decreased by 9.8% (p < 0.05) and 8.3% (p = 0.05), respectively, over 45 months. In a comparison group matched for age, sex, and chronic Pseudomonas aeruginosa infection but no increase in antibody titers, FVC and FEV1 were unchanged. The results indicate that wild-type adenovirus infections are prevalent in cystic fibrosis patients and that wild-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 when using adenoviral vectors for gene therapy.
Rosenecker
J
J
Universitätskinderklinik im Dr. von Haunerschen Kinderspital, Munich, Germany.
Harms
K H
KH
Bertele
R M
RM
Pohl-Koppe
A
A
v Mutius
E
E
Adam
D
D
Nicolai
T
T
D000257:Adenoviridae Infections / Q000097:blood / Q000276:immunology*; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications / Q000276:immunology / Q000821:virology*; D005260:Female; D005541:Forced Expiratory Volume; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007223:Infant; D008297:Male; D011446:Prospective Studies; D014407:Tumor Cells, Cultured; D014797:Vital Capacity
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M