5.3 Baseline Adenovirus -related Data from Individuals with CF Relevant to 
Administration of a Replication Deficient Recombinant Adenovirus 
During the baseline period of the protocol, baseline parameters relevant to 
the adenovirus vector will be evaluated, including baseline immunity against 
type 5 adenoviruses, the presence of infectious viruses in the respiratory 
tract, the baseline inflammation in the respiratory tract, and the presence of 
type 5 adenovirus Ela sequences in the respiratory tract. 
5.3.1 Anti -Adenovirus Antibodies in Blood and Lung of Individuals with CF 
Consistent with data demonstrating that most adults have some antibodies 
against adenovirus type 5 in serum (Strauss, 1984), evaluation of the 
individuals with cystic fibrosis entering the protocol will likely demonstrate 
circulating antibodies against adenovirus. It is also possible that anti- type 
5 adenovirus antibodies will be detected in the respiratory epithelial lining 
fluid (ELF) of the individuals with cystic fibrosis. However, even if present, 
it is unlikely that anti -adenovirus antibodies on the respiratory epithelial 
surface will be active, as: (1) almost all individuals with CF have active 
neutrophil elastase in CF respiratory ELF; (2) neutrophil elastase will cleave 
immunoglobulins; and (3) there is in vivo evidence that immunoglobulins in ELF 
from individuals with CF are cleaved (Fick et al . , 1984). Despite the unlikely 
possibility that such antibodies could survive in CF ELF, studies will be done 
during the baseline period to determine whether anti- type 5 adenovirus 
antibodies are present in the serum and lung of the individuals with CF, and 
if detectable, whether such antibodies are neutralizing. 
5.3.2 Infectious Viruses In the Respiratory Tract of Individuals with CF 
To minimize the risks for recombination or complementation of AdCFTR with an 
intercurrent respiratory virus infection, all individuals will be screened 
during the baseline period for infection with respiratory viruses in the 
respiratory tract. The absence of such an infection will be an inclusion 
criterion (see Section 5.4.1). This criterion was established based on 
screening of individuals with CF for such viruses. 
Individuals with CF (n=17 evaluation for all viruses, all sites; n=21 total) 
were screened in the respiratory tract (nasal brushing, bronchial brushing, 
and bronchoalveolar lavage) for the presence of: adenovirus (all serotypes 
except 40, 41), cytomegalovirus, varicella zoster virus, herpes simplex 
viruses I and II, influenza A and B, parainfluenza 1, 2 and 3, and respiratory 
syncytial virus. Control groups included normal non-smokers, normal smokers, 
and individuals with alpha 1-antitrypsin deficiency. 
All cultures in the control groups were negative for all sites and all 
viruses . All CF individuals were negative for adenovirus , cytomegalovirus , 
varicella zoster virus, influenza A and B, parainfluenza 1, 2 and 3, and 
respiratory syncytial virus at all sites. Two of 17 (12%) of individuals with 
CF had culture evidence of herpes simplex virus [one individual in bronchial 
epithelium and respiratory epithelial inflammatory cells (bronchoalveolar 
lavage) , one individual in lavage only, both were negative in the nasal 
epithelium]. See Table 4.9-D for details. 
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Recombinant DNA Research, Volume 16 
