transmitted by the respiratory, oral, or conjunctival routes. The incu- 
bation period ranges from 5-10 days with an average of 7 days. 
The immune/inflammatory system contains and clears adenovirus infections 
through a variety of interactions involving humoral and cellular processes . 
Although humoral responses can modify the course of adenovirus infection, 
it is clear that cell -mediated immune mechanisms are central to the 
containment and resolution of these infections (Straus, 1984). Lower respi- 
ratory tract infection with frank pneumonia is uncommon with adenovirus 
infection; when it does occur in adults it is almost always associated with 
adenovirus subtypes 3, 4, 7, and 21, not 5. There are rare fatalities with 
adenoviral infection; almost all cases of devastating adenovirus infections 
have been documented in circumstances in which there is inadequate cellular 
immunity, including neonates, immune -depressed individuals with cancer, 
transplants, HIV infection, and individuals receiving corticosteroids, 
cytotoxic drugs or radiation, and children with T-cell disorders (Horwitz, 
1990a; Straus, 1984; Hierholzer, 1992). There is no evidence that children 
or adults with CF have increased susceptibility to or severity of adenovi- 
rus infection. 
Despite the fact that all subgroups of adenovirus can transform cells from 
various species in vitro and some subgroups (A and B) can induce tumors in 
newborn hamsters, there is no evidence that any adenovirus type is asso- 
ciated with human tumors in vivo (Horwitz, 1990a; Straus, 1984). The vec- 
tors AdCFTR and AvlCFl are based on adenovirus type 5 , a member of subgroup 
C, a subgroup that does not produce tumors in any animal in vivo (Horwitz, 
1990a; Straus, 1984). 
Because of the widespread prevalence of adenovirus infection in closed 
populations such as military recruits, considerable effort was put into 
developing adenovirus vaccines. In 1963, live adenovirus vaccines were 
developed using enteric-coated capsules containing adenovirus types 4 and 7 
(Chanock et al. , 1966; Edmondson et al . , 1966; Gutekunst et al., 1967; 
Smith et al . , 1970; Top et al., 1971b; Top et al . , 1971c). These vaccines 
cause inapparent enteric infection. There is no spread of infection to the 
respiratory tract or evidence of respiratory symptoms. Spread to non- 
infected individuals is rare. The oral vaccines elicit serum but not local, 
neutralizing antibodies on the nasal epithelial surface (Scott, 1972; 
Smith, 1970). Since the initial development of these vaccines, their use is 
widespread in the military, with bivalent (Ad4, Ad7) live enteric vaccines 
in general use in the US and other militaries around the world. It is 
estimated that >5 million individuals have had live adenoviruses 
administered in this form (Chanock et al . , 1966; Couch et al . , 1963; A. 
Davis, personal communication; Top et al., 1971b; Top et al . , 1971c). 
2.2 Structure of the Adenovirus 
The structure of the adenovirus is conveniently described on the basis of 
the adenovirus genes expressed following infection of human cells. By 
convention, the 36 kb of adenovirus DNA is divided into 100 map units (mu) ; 
360 bp/mu. The viral genome is transcribed in two major stages, an early 
(E) phase which precedes viral DNA replication and a late (L) phase (start- 
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