for details). Rhesus (5. 1-8. 3 kg) were exposed to AdRSV./9gal (2-6xl0 9 
pfu/kg, n=6) or vehicle (as controls, n=3) (rhesus study 1C pre-challenge 
phase, 2C pre-challenge phase, and 3C) . The animals have been followed for 
21 to 135 days (day 21-2 treated, 1 control; day 28-2 treated, 1 con- 
trol; day 135 - 2 treated, 1 control). No deaths have occurred. There were 
no observed changes in any animals or between the groups in: general behav- 
ior, physical exam, vital signs, complete blood counts, detailed serum 
chemistries, arterial blood gases, chest X-ray and lung compliance (all 
parameters evaluated before day 0 and at days 0, 3, 7, 14, 21, 28 and then 
at 2 weekly intervals). For the animals evaluated up to 21 and 28 days, 
bronchoalveolar lavage was carried out at day 0, 3, 7, 14, 21 or 28. There 
was no difference in the numbers or type of inflammatory cells recovered 
(animals compared to controls) and all parameters remained within the 
normal range. 
A similar study is presently ongoing in rhesus receiving AvlCFl (2xl0 10 /kg 
to the right mainstem bronchus; n=4 treated; n=l control) (rhesus study 4C 
pre - challenge , 5C pre - challenge) . After 3 months all animals are alive and 
there is no change in their general behavior, physical exam, vital signs, 
complete blood counts, detailed serum chemistries, arterial blood gases, 
chest X-ray, and lung compliance. Bronchoalveolar lavage was done on days 
0, 3, 7, 14, 21, 28, 42, 56 and 83. There were no significant differences 
between control and treated animals in cell number or types of inflammatory 
cells recovered. 
From the studies in nonhuman primates, it appears that no significant 
inflammatory response occurs on the respiratory epithelial surface follow- 
ing respiratory administration of a recombinant adenovirus over a 3 to 4 
week period. Consistent with these observations, there are no changes in 
any clinical parameters including those related to the lung. Although it is 
possible that vector administration to the rhesus did have a non- epithelial 
(e.g., blood vessel or airway interstitial) inflammatory response not de- 
tected by the lavage, the lack of any abnormalities in clinical parameters 
suggests that there may be species to species variations in the responses 
to the vector. Further, if inflammatory responses do occur, they do not 
appear to have significant clinical relevance. 
From the available data it is impossible to determine whether the individu- 
al with mild to moderate CF will respond to respiratory administration of 
the vector in a fashion closer to the cotton rat or to the rhesus. Further, 
if there is a transient inflammatory response, it should be put in context 
that the airways of individuals with CF are chronically inflamed, with a 
neutrophil-dominated inflammatory process that is very intense, far beyond 
that of any other chronic disorder. Quantitative assessment of this inflam- 
mation can be obtained by bronchial brush (to assess the epithelium) 
and bronchoalveolar lavage (to assess the inflammation in the epithelial 
lining fluid). The results demonstrate a marked neutrophil - dominated in- 
flammation in the airway epithelium of individuals with CF (Table 4.4-A). 
It is unlikely that this ongoing chronic inflammation will be significantly 
influenced by a transient response to the vector should it occur. 
4.5 Are Anti-Vector Antibodies Elicited by Respiratory Administration of 
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