at 7 days at 14 days 
4 positive 
for adenovirus 
4 positive 
for adenovirus 
pharvnx 
rectum 
pharvnx 
rectum 
vehicle at 0 time 
0/3 
0/3 
vehicle at 0 times, 
vehicle at 7 days 
0/2 
0/2 
vehicle at 0 time 
Ad5 at 7 days 
2/4 
0/4 
AvlCFl at 0 time 
0/3 
0/3 
AvlCFl at 0 time , 
vehicle at 7 days 
0/5 
0/5 
AvlCFl at 0 time , 
0/3 
0/3 
Ad5 at 7 days 
Thus, while exposure to Ad5 alone resulted in Ad5 shedding 7 days later, 
pre-exposure to AvlCFl did not. This is consistent with the concept that 
E1“E3~ adenovirus vectors will suppress wild type replication (see Section 
4.9) and that it is not a danger to the environment. To evaluate shedding 
of recombinant replication deficient adenovirus vector (AdRSV./Sgal) in 
rhesus, adenovirus was administered to airways of 3 groups of rhesus mon- 
keys (rhesus study 1C, 2C and 3C) , each group composed of 1 control (re- 
ceiving vehicle) and 2 adenovirus treated animals. Groups 1 and 2 had 
adenovirus (2-8xl0 9 pfu/kg) delivered to the right mains tem bronchus on 
days 0 and 21 or 28. Group 3 has adenovirus delivered to the trachea (and 
held in place by balloon tamponade for 30 minutes) on day 0 and day 135. 
Animals were serially followed (weekly for one month, then bi-weekly, then 
monthly) for shedding for up to 187 days by obtaining whole blood, lower 
airway lavage with sterile saline, and swabs from posterior pharynx and 
rectum. To detect adenovirus, samples were cultured on 293 [which allows 
the growth (and hence detection) of adenovirus with or without the Ela 
region] and A549 cells (which allows the growth only of adenovirus contain- 
ing the Ela region, i.e., replication competent adenovirus). The recombi- 
nant Ela deficient adenovirus vector (but not replication competent adeno- 
virus) was detected in secretions of 1 animal in groups 1 and 2; on day 3 
in fecal samples and lung lavage, and day 43 (15 days after receiving a 
second dose of the same adenovirus) in lung lavage only. In group 3, Ela 
deficient adenovirus was detected in the lung lavage and rectum fecal 
samples of 2 treated animals at day 3 after which it was not detected 
during a 46 day follow-up period. 
Adenovirus shedding following AvlCFl administration was also evaluated. As 
with AdRSV.^gal, AvlCFl (2X10 10 was administered to the large airways of 
rhesus monkeys (rhesus studies 4C and 5C) . In rhesus study 4C , vehicle 
(n=l) or AvlCFl (n=2) was delivered to the right mainstem bronchus at day 
zero. Animals were evaluated weekly for 42 days, then biweekly, for up to 
56 days for the presence of adenovirus in blood (days 0-7 only), respirato- 
Recombinant DNA Research, Volume 16 
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