ABSTRACT
These attractive features have pushed Ad vectors to the forefront as vehicles for vaccine delivery. However, a significant concern in all rAd vaccine approaches is whether prior immunity to the vector, or anti-vector immunity induced as a result of immunization, will minimize the effectiveness of Ad vaccination. This concern arose principally as a result of gene therapy studies in which rAds were administered repeatedly at high dosages to maintain persistent expression of the therapeutic transgene. The result was development of vector immunity, which ultimately precluded continuous effective treatment (19,20). The extent to which such vector immunity will impact the utility of Ad-recombinant vaccines is currently not known and depends in part on the number and dosages of immunizations necessary to elicit the desired level of adaptive immunity. In principle, vaccination regimens should require lower doses of immunogen, administered infrequently to elicit immune memory responses. Nevertheless, several approaches have been exploited to circumvent this potential problem and will be discussed in this chapter. These alternatives include the use of alternate serotypes, Ad vectors of nonhuman origin, and chimeric Ad vectors in which neutralizing epitopes on the virion surface have been substituted with epitopes representing rare Ad serotypes.
