Attenuated mutants of Salmonella typhimurium containing a strongly selectable vector plasmid designed for insertion and expression of foreign DNA will be tested as potential live oral vaccines for pertussis. Near-isogenic strains attenuated by either aro A or cya/crp deletions, and deleted for the asd gene (causes requirement for diaminopimelic acid, DAP) will be used as carriers for derivatives of asd encoding plasmid pYA248 containing insert DNA. Plasmids which allow expression of B. pertussis filamentous hemagglutinin (FHA), FHA plus nontoxic portions of pertussis toxin (PT), and FHA plus another nontoxic surface antigen will be constructed. Mice will be fed the attenuated vaccine strains containing chimeric plasmids, and evaluated for the following: plasmid stability in orally challenged mice; Salmonella survival and multiplication in mice; elicitation of specific (anti- Bordetella pertussis antigenic) secretory antibodies in mice; elicitation of specific serum antibodies in mice; elicitation of specific cellular immune responses in mice; and protection of mice from intranasal challenge with B. pertussis.
| Molina, N C; Parker, C D (1990) Murine antibody response to oral infection with live aroA recombinant Salmonella dublin vaccine strains expressing filamentous hemagglutinin antigen from Bordetella pertussis. Infect Immun 58:2523-8 |
| Williams, M E; Lichtman, A H; Abbas, A K (1990) Anti-CD3 antibody induces unresponsiveness to IL-2 in Th1 clones but not in Th2 clones. J Immunol 144:1208-14 |
