Adenovirus Vectors Composed of Subgroup B Adenoviruses

Fuminori Sakurai; Kenji Kawabata; Hiroyuki Mizuguchi

Abstract

Recombinant adenovirus (Ad) vectors have gained attention as gene delivery vehicles because they efficiently introduce foreign DNA into host cells, can be produced in high titers, and are able to transduce terminally differentiated cells. Conventional Ad vectors commonly used in the world, including clinical trials, are derived from subgroup C Ad serotype 5 (Ad5). Although Ad5 vector-mediated transduction provides encouraging results, preclinical and clinical applications have revealed several disadvantages of Ad5 vectors, such as high seroprevalence of anti-Ad5 antibodies in adults and low transduction efficiencies of Ad5 vectors in cells lacking the primary receptor for Ad5, the coxsackievirus and adenovirus receptor (CAR). To overcome these problems, novel recombinant Ad vectors, which are derived entirely from subgroup B Ads, including Ad serotypes 3, 7, 11, and 35, have been developed. These subgroup B Ad vectors can infect cells via human CD46 (membrane complement protein), which is ubiquitously expressed in almost all human cells, and/or via unidentified receptors other than CAR, leading to efficient transduction of subgroup B Ad vectors in most human cells, including CAR-negative cells. In addition, transduction efficiencies of subgroup B Ad vectors do not decrease in the presence of anti-Ad5 antibodies, and seroprevalences of most subgroup B Ads are lower than that of Ad5, indicating that transduction with subgroup B Ad vectors is unlikely to be hampered by preexisting anti-Ad antibodies. In this paper, we review the advances in subgroup B Ad vector research.

Keywords: Adenovirus vector, gene therapy, transduction, neutralizing antibodies, CD46, fiber, seroprevalence, coxsackievirus and adenovirus receptor (CAR), receptors