M.J. Welsh and A.E. Smith, RAC Application 
of spread to another person, c) Our data suggest that the sentinal monkey was not exposed 
to the adenovirus, d) Studies using live wild-type adenovirus vaccines show little 
horizontal transmission between roommates (146). 
B.4.c. What precautions will he taken against such spread (e.g., to patients sharing a room, 
health-care workers or family members) ? 
We will take several precautions to minimize the possibility of spread. 
The amount of virus that will be applied is very small; thus the possibility of transfer is 
minimized. 
Hospital care will be administered by trained health-care workers. The nurses and care 
givers in the University of Iowa Clinical Research Center are skilled at precisely following 
experimental protocols. In addition, we have sought the advice of Dr. Richard Wenzel, 
M.D., Hospital Epidemiology, and Ms. Marlene Schmid, Senior Nurse Epidemiologist, in 
minimizing the possibility of spread of the virus. We will follow their recommendations 
(Appendix 4). Healthcare workers will be informed of the nature of the study and of the 
potential risk to immunocompromised persons they may also care for. 
To minimize the risk of exposure to persons other than the participant, the patient will be 
kept in isolation in a hospital room in the Clinical Research Center. Persons coming in 
contact with the participant will practice hand washing and use gowns, gloves, and masks, 
which will be removed upon leaving the room. 
In addition to the strict control placed on the exposure of the patient to his/her 
surroundings, as previously discussed, Ad2/CFTR-1 is defective and because of its large 
size, difficult to package. Thus, its ability to replicate on its own is doubly compromised. 
The participant will not be discharged from the isolation room until there are two 
consecutive nasal swabs that are negative for live virus. If the nasal swabs and brushes 
should remain positive for recombinant adenovirus for 4 weeks after infection and if the 
patient is showing no adverse clinical effects, we will discharge them from the hospital at 
that point. We will, however, continue to evaluate them at weekly intervals. We believe 
that to continue to confine the patient to the room at that point would be inhumane. 
Moreover, if no adverse effects have been observed, the risk to the general public and the 
environment should be minimal. Most importantly in this regard, our safety studies in 
cultured cells and in animals and reports from the literature suggest that the possibility that 
the patient will continue to shed virus or pass it to another person is remote (146). 
B.4.d. What measures will be undertaken to mitigate the risks, if anv. to public health ? 
The measures are described above in section B.4.c. 
B.4.e. In light of possible risks to offspring, including vertical transmission, will birth 
control measures be recommended to the patient? Are such concerns applicable to 
health care personnel? 
As described in the inclusion and exclusion criteria for patient selection, all participants 
must practice contraception for at least one month before and after the protocol. Greater 
than 97% of men with CF are sterile. Women participants must have a negative pregnancy 
test. Given the exceedingly low theoretical risk, the results of our animal experiments 
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