LT(R192G), A NONTOXIC MUTANT OF THE HEAT-LABILE ENTEROTOXIN OF ESCHERICHIA-COLI, ELICITS ENHANCED HUMORAL AND CELLULAR IMMUNE-RESPONSES ASSOCIATED WITH PROTECTION AGAINST LETHAL ORAL CHALLENGE WITH SALMONELLA SPP

In the current study we examined the ability of a novel mucosal adjuva nt, LT(R192G), to enhance the humoral and cellular immune responses ag ainst killed Salmonella spp. and to affect protection against lethal o ral challenge with wild-type organisms. Mice orally immunized with kil led S. dublin in conjunction with LT(R192G) were protected against let hal oral challenge and had higher IFN-gamma IL-2 and IgG responses tha n did mice orally immunized with killed S. dublin alone which were not protected This study demonstrates that the function of LT(R192G) in p rotection against typhoid-like disease is to upregulate/enhance the Th 1 arm of the immune response against killed organisms. When used as a mucosal adjuvant, LT(R192G) enables the use of killed bacteria or viru ses as vaccines by enhancing the overall humoral and cellular host imm une response to these organisms, especially the Th1 arm of the immune response. These findings have significant implications for vaccine dev elopment and further support the potential of LT(R192G) to function as a safe, effective adjuvant for mucosally administered vaccines. (C) 1 998 Elsevier Science Ltd. All nights reserved.