Date of Award
1993
Degree Type
Dissertation
Degree Name
Doctor of Philosophy
Abstract
Schistosomiasis, a chronic and debilitating parasitic disease, infects an estimated 200 million people and causes 750,000 deaths a year. Therefore, the development of an effective vaccine is of high priority for the control of this disease.;The surface of the syncytial epithelium of Schistosoma mansoni consists of an apical plasma membrane and an overlying envelope. The rapid turnover of these membranes in response to the host's attack is considered to be one of the mechanisms by which this parasite escapes the effects of the host's immune system. Our approach has been to identify surface components which play a pivotal role in this evasion mechanism and target functional important antigens as possible vaccine candidates against schistosomiasis.;The third component of Complement (C{dollar}\sb3{dollar}) has previously been shown to stimulate the synthesis of the EN via a Ca{dollar}\sp{lcub}2+{rcub}{dollar}-dependent signal transduction mechanism. The present study was designed to identify and characterize a C{dollar}\sb3{dollar} receptor on the schistosome surface.;Using rosette assays a C{dollar}\sb3{dollar} binding site was found present in the older stages of schistosome development, and with immunolabelling microscopy the C{dollar}\sb3{dollar} binding site was localized on the dorsal surface of male parasites. ELISAs performed on isolated surface membranes shown that the C{dollar}\sb3{dollar} binding site is restricted to the envelope fraction. Crosslinking experiments demonstrated that a 130 kD envelope polypeptide is the C{dollar}\sb3{dollar} receptor, and metabolic labelling studies proved that the receptor is synthesized by the schistosomes and not adsorbed from the host. Antibodies raised against this receptor were able to block envelope synthesis in vivo, confirming the function of this receptor in envelope synthesis. Immunological cross-reaction studies have demonstrated the presence of the C{dollar}\sb3{dollar} receptor on S. haematobium and S. mansoni.;In conclusion, the C{dollar}\sb3{dollar} receptor by virtue of its accessibility on the surface, its immunogenicity, and its function in membrane turnover, should be an excellent experimental vaccine candidate against schistosomiasis. Furthermore, it is the first time that an envelope component was identified and can be used as a marker for the envelope.
Recommended Citation
Silva, Erika Eliana, "Characterization Of A Schistosoma Mansoni C(3) Receptor As A Potential Vaccine Candidate" (1993). Digitized Theses. 2259.
https://ir.lib.uwo.ca/digitizedtheses/2259