This proposal describes experiments to develop a defined vaccine against schistosomiasis for use in humans. In pursuit of this goal, laboratory animals will be vaccinated with purified antigens, antigen fragments, synthetic peptides, and fusion proteins produced by recombinant DNA technology.
The specific aims of this proposal are: 1) to study via vaccination trials in mice, the protective potential of 3 distinct surface membrane antigens when administered singly or in combination; 2) to test whether fusion proteins which express epitopes found on the 3 surface antigens can induce protective immunity in mice; 3) to map the epitopes detected by antibodies on the 3 native surface antigens, and then test whether antigen fragments and/or synthetic peptides are immunogenic in vivo; 4) to test if mice become sensitized to eggs and egg antigens after vaccination with native, recombinant or synthetic antigens. The three surface membrane antigens were selected with protective monoclonal antibodies produced from mice. All three antigens can be purified by immunoaffinity chromatography and/or electroelution. Epitopes will be mapped using both protective monoclonal antibodies and monospecific antisera as probes. Antigens will be fragmented into peptides by treatment with cyanagen-bromide and other proteases. Antigen fragments will be purified by reverse-phase HPLC, or by electro-elution after SDS-PAGE. Fusion proteins to be tested were produced by recombinant cDNA clones selected from adult worm and cercarial tail cDNA libraries using lambda gtll as expression vector. Assays for sensitization to antigens will be done by both lung and liver granuloma assays.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
1R22AI024557-01A2
Application #
3444972
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1988-07-01
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Public Health
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
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Reynolds, S R; Dahl, C E; Harn, D A (1994) T and B epitope determination and analysis of multiple antigenic peptides for the Schistosoma mansoni experimental vaccine triose-phosphate isomerase. J Immunol 152:193-200
Richter, D; Reynolds, S R; Harn, D A (1993) Candidate vaccine antigens that stimulate the cellular immune response of mice vaccinated with irradiated cercariae of Schistosoma mansoni. J Immunol 151:256-65
Chikunguwo, S M; Quinn, J J; Harn, D A et al. (1993) The cell-mediated response to schistosomal antigens at the clonal level. III. Identification of soluble egg antigens recognized by cloned specific granulomagenic murine CD4+ Th1-type lymphocytes. J Immunol 150:1413-21
Richter, D; Harn, D A (1993) Candidate vaccine antigens identified by antibodies from mice vaccinated with 15- or 50-kilorad-irradiated cercariae of Schistosoma mansoni. Infect Immun 61:146-54
Richter, D; Incani, R N; Harn, D A (1993) Isotype responses to candidate vaccine antigens in protective sera obtained from mice vaccinated with irradiated cercariae of Schistosoma mansoni. Infect Immun 61:3003-11
Reynolds, S R; Shoemaker, C B; Harn, D A (1992) T and B cell epitope mapping of SM23, an integral membrane protein of Schistosoma mansoni. J Immunol 149:3995-4001
Harn, D A; Gu, W; Oligino, L D et al. (1992) A protective monoclonal antibody specifically recognizes and alters the catalytic activity of schistosome triose-phosphate isomerase. J Immunol 148:562-7
Shoemaker, C; Gross, A; Gebremichael, A et al. (1992) cDNA cloning and functional expression of the Schistosoma mansoni protective antigen triose-phosphate isomerase. Proc Natl Acad Sci U S A 89:1842-6