CONSTRUCTION OF LIVE ATTENUATED SHIGELLA VACCINE STRAINS THAT EXPRESS CFA/I ANTIGENS (CFAB AND CFAE) AND THE B SUBUNIT OF HEAT-LABILE ENTEROTOXIN (LTB) FROM ENTEROTOXIGENIC E. COLI

摘要

We have constructed a prototype vaccine strain of Shigella flexneri 2a (SC608) that can serve as a vector for the expression and delivery of heterologous antigens to the mucosal immune system. SC608 is an asd derivative of SC602, a well-characterized vaccine strain, which has recently undergone several phase 1 and 2 trials for safety and immunogenicity. Using non-antibiotic asd-based plasmids, we have created novel constructs for the expression of antigens from enterotoxigenic E. coli (ETEC), including CFA/I (CfaB and CfaE) and the B-subunit from heat-labile enterotoxin (LTB) in Shigella vaccine strain SC608. The initial experiments demonstrate the validity of a multivalent invasive Shigella strain that can serve as a vector for the delivery of pathogen-derived antigens.