Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI025055-02
Application #
3138389
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1989-03-01
Project End
1992-02-29
Budget Start
1990-03-01
Budget End
1991-02-28
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
University of Missouri-Columbia
Department
Type
Schools of Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211