Enhanced immune responses to viral epitopes by combining macrophage-inducible expression with multimeric display on a Salmonella vector

In this study, the immunogenicity of chimeric 987P fimbriae on a Salmonella vaccine strain was improved by optimizing fimbrial expression. The constit utive tetA promoter and the in vivo activated nirB and pagC promoters were evaluated for their use to express two epitopes of the transmissible gastro enteritis virus (TGEV) spike protein carried by fimbriae which were display ed on a Salmonella vaccine strain. Constructs with the pagC promoter were s hown to drive increased expression of chimeric 987P fimbriae in macrophages as well as in Mg2+ -poor media, mimicking a major environmental signal fou nd in Salmonella-containing endocytic vacuoles of macrophages. Mice immuniz ed orally with a Salmonella vaccine strain which expressed chimeric fimbria e from the pagC promoter elicited significantly higher mucosal and systemic immune responses to both the 987P fimbriae and the TGEV epitopes than mice immunized with the same strain hosting a tetA or nirB promoter-driven expr ession plasmid. Moreover, only the Salmonella vaccine strains harboring a p lasmid with the pagC promoter, with or without an additional tetA promoter in tandem, elicited neutralizing antibodies to TGEV. This indicated that th e pagC promoter can be used successfully to improve epitope-display by chim eric fimbriae on Salmonella vaccine strains for the induction of a desired immune response. (C) 2001 Elsevier Science Ltd. All rights reserved.