The goals of this research are to contribute to the complete understanding of the pathogenesis and immunology of cholera at both the organismal and the molecular levels with the expectation that this will lead to the development of rational and effective means of immunoprophylaxis. As cholera is the prototype of an expanding number of enterotoxic enteropathies, the observations are pertinent to the larger global problem of secretory diarrheal disease. It is clear that the disease, cholera, is an effective immunizing process which presents to the human host a consortium of products elaborated by the cholera vibrios growing in vivo. These include: colonization factors (as yet undefined); surface components such as the lipopolysaccharide and outer membrane proteins; the HA/protease; other enzymes; the mannose-sensitive (El Tor biotype) and other hemagglutinins; the flagellum; and the enterotoxin. This proposal specifically addresses: the identification and characterization of factor(s) participating in adherence of Vibrio cholerae to intestinal epithelium; outer membrane antigens (particularly novel iron-regulated proteins expressed in vivo); and the definition of antigens and antibodies which may be protective [including functional domains and epitopes on the immunodominant, binding, choleragenoid (B-subunit pentamer) portion of the cholera enterotoxin]. Technology includes: bacterial binding studies; protein separation and analysis with SDS-PAGE and immunoblotting; micro-antibacterial assays involving protein components of mothers' milk, polyclonal and monoclonal antibacterial antibodies; and antitoxic monoclonal antibodies and synthetic peptides of the cholera enterotoxin with the objective of developing a synthetic vaccine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI017312-11
Application #
3566213
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1980-04-01
Project End
1991-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
11
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
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Jouravleva, E A; McDonald, G A; Garon, C F et al. (1998) Characterization and possible functions of a new filamentous bacteriophage from Vibrio cholerae O139. Microbiology 144 ( Pt 2):315-24
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Boesman-Finkelstein, M; Peterson, J W; Thai, L S et al. (1996) A nontoxic chimeric cholera toxin analog. Ann N Y Acad Sci 797:266-8
Boesman-Finkelstein, M; Peterson, J W; Thai, L S et al. (1996) A nontoxic cholera enterotoxin (CT) analog is chimeric with regard to both epitypes of CT-B subunits, CT-B-1 and CT-B-2. Infect Immun 64:346-8
Sengupta, D K; Boesman-Finkelstein, M; Finkelstein, R A (1996) Antibody against the capsule of Vibrio cholerae O139 protects against experimental challenge. Infect Immun 64:343-5
Hase, C C; Thai, L S; Boesman-Finkelstein, M et al. (1994) Construction and characterization of recombinant Vibrio cholerae strains producing inactive cholera toxin analogs. Infect Immun 62:3051-7
Hase, C C; Bauer, M E; Finkelstein, R A (1994) Genetic characterization of mannose-sensitive hemagglutinin (MSHA)-negative mutants of Vibrio cholerae derived by Tn5 mutagenesis. Gene 150:17-25

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