ORAL DELIVERY OF FOREIGN ANTIGENS BY ATTENUATED SALMONELLA - CONSEQUENCES OF PRIOR EXPOSURE TO THE VECTOR STRAIN

Several strains of Salmonella have been used as vectors for the delive ry of Escherichia coli fimbrial proteins to the gut-associated lymphoi d tissue (GALT) of the mouse. Plasmids carrying a complementing thyA() gene, together with genes specifying synthesis of K88 or K99, were i ntroduced into non-reverting thyA Salmonella mutants. The resulting co nstructs expressed the foreign pilin protein on their surfaces and, pr ovided the vector was able to colonize rite GALT, elicited strong seru m responses to K88 or K99. These responses were dramatically impaired however, in recipients with pre-existing immunity to the vector strain . Mice initially infected with Salmonella stanley ca 4, 10 or 20 weeks prior to oral administration of S. stanley-K88 showed greatly reduced serum responses to K88 as determined by ELISA. The hypo-responsivenes s seen in vector-printed mice could be largely overcome by changing th e serotype of the strain subsequently used to deliver the foreign prot ein. Copyright (C) 1997 Elsevier Science Ltd.