This project focuses on a vaccine candidate MSP 119 which is present in the asexual blood stages of the malaria parasite's lifecycle. Immunisation with MSP 119 has been shown previously to protect against growth of the blood stage parasite. Previous studies have shown there are three types of antibodies produced against Plasmodium falciparum MSP 119: inhibitory, blocking and neutral with only inhibitory antibodies giving protection. It is vital to identify the epitopes recognised by inhibitory antibodies to engineer an effective vaccine. The aim of this project is to map the antibody binding sites of Plasmodium yoelii (a rodent parasite) MSP119. Three protective Plasmodium yoelii MSP119 specific monoclonal antibodies that had been created previously were used. MSP119 variants containing amino acid changes in residues 12, 16, 17 and 28 were created and binding to the monoclonal antibodies was investigated using western blotting, ELISA and surface plasmon resonance analysis. This showed that all four residues were involved in antibody binding. A comparison of the residues found to be important for MSP119 antibody binding in Plasmodium yoelii and inhibitory antibody binding in Plasmodium falciparum show they lie within the same area. This suggests there are conserved areas for inhibitory antibody binding across the species implying a common mechanism of action. Immunisation studies with the MSP 119 variants have shown that changes to residue 28 abolish the protective immune response to challenge infection with Plasmodium yoelii YM seen with wildtype MSP 119. Structural NMR studies of wildtype and MSP119 variants have shown that residue 28 plays a vital structural role. The information presented in this project could be important in developing antigens for vaccination to specifically stimulate production of inhibitory antibodies. It could help direct research into understanding the mechanism of action of inhibitory antibodies and aid in the development of new therapeutic strategies targeting MSPI19.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:674650 |
| Date | January 2008 |
| Creators | Curd, Rachel Dawn |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1445223/ |
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