A genomic sequence encoding an S. mansoni surface glycoprotein antigen family has been identified in this laboratory. The long term objectives of this proposal are directed towards expressing parasite DNA sequences using a recombinant vector system, for the purpose of assessing the efficacy of the recombinant protein products as protective vaccines against human schistosome infections, initially in a rat model but subsequently in other test systems. To accomplish these objectives, information is required pertaining to the possible stage-specific expression of different members of this antigen family, which could provide a mechanism to explain the phenomenon of concomitant immunity in the rat model. Monospecific antibodies will be prepared against putative peptide epitopes on the form of protein antigen expressed in adult worms and used to probe the surfaces of larval and adult stages. These antisera will also be tested for their efficacy to protect rats against a cercarial infection. The possibility of differential transcription of the gene in larval and adult stages will be examined by recombinant DNA techniques. Vaccination with recombinant products from expression vectors, constructed from DNA sequences of the gene, will be the ultimate objective. The following specific aims (grouped into 3 subject areas) are designed to accomplish these objectives over a 5- year period: I. Immunochemistry (1) Prepare protein conjugates of candidate epitope synthetic peptides; immunize mice, rats, & rabbits. (2) Use anti-peptide sera for immunofluorescence assays on parasites of different developmental stages. (3) Test efficacy of strongest antisera to protect rats or mice from infection; determine target stage. (4) Prepare hybridomas and use monoclonal antibodies to define target peptide fine-structure. II. Molecular Biology (1) Using synthetic probes based upon genomic sequences, hybridize with mRNA of different stages. (2) Prepare cDNA libraries, select clones using appropriate probes, and sequence the cDNA. (3) Express in recombinant vectors the cDNA from target larval stage or genomic DNA sequences which lack introns. Test protein products as protective vaccines. III. Vaccination (1) Immunize rats and other species with recombinant protein and assess relative efficacies as protective vaccines. Distinguish protective from immunopathological immune responses. (2) Analyze epitope recognition by B and T cells to improve vaccine efficacy.
| Bungiro Jr, R D; Goldberg, M; Suri, P K et al. (1999) Interleukin-12 as an adjuvant for an antischistosome vaccine consisting of adult worm antigens: protection of rats from cercarial challenge. Infect Immun 67:2340-8 |
| Suri, P K; Goldberg, M; Madikizela, M et al. (1997) Evaluation of recombinant protein r140, a polypeptide segment of tegumental glycoprotein Sm25, as a defined antigen vaccine against Schistosoma mansoni. Parasite Immunol 19:515-29 |
