ABSTRACT

The unique predominance of IncHI1 plasmids found naturally among clinical isolates of S. Typhi suggests that stable maintenance of unrelated expression plasmids introduced into such strains may not be straightforward. Therefore, the further development of attenuated and clinically acceptable S. Typhi vaccine strains into live vectors carrying engineered plasmids expressing foreign antigens becomes problematic. Reengineering of IncHI1 replicons for use as expression plasmids, although theoretically feasible, has, to date, not been attempted. In addition, the copy number of these plasmids is one to two copies per chromosomal equivalent and, therefore, provides little advantage over chromosomal integration systems for expressing heterologous antigens.