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Title: Immunopotentiation of malaria vaccines
Author: Russell, Clare
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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Plasmids were constructed to encode C3d/PfEMP-1 fusions and expression of recombinant protein in mammalian cells in culture was assayed. Eukaryotic expression of P. falciparum proteins proved to be problematic and a re-condoning approach was adopted to address this. The production of polyclonal anti-PfEMP-1 antibodies in mice was assessed in immunofluorescence assays and in immunoblots with P. falciparum-infected erythrocytes. The data question the suitability of a DNA vaccine approach in the development of a PfEMP-1-based vaccine using C3d. In order to raise specific antibodies to PfEMP-1 and to develop a suitable assay to assess immunogenicity of this antigen, research efforts became focussed on the production of recombinant PfEMP-1 protein, with a view to immunising mice. A recombinant PfEMP-1 domain was expressed in mammalian cells and characterised, demonstrating it to be the ligand involved in binding uninfected erythrocytes. Its reactivity with immune sera and, therefore, its suitability as a malaria vaccine candidate was assessed. Findings highlight the need for further work on the development of methods to produce functionally active recombinant protein. They also show the necessity of improving methods of detecting surface expression of PfEMP-1. The suitability of the Saimiri monkey model for C3d-based vaccination and P. falciparum challenge experiments was assessed. In other species, the receptor for C3d is CR2, expressed on B cells. Saimiri B cells were characterised and their capacity to bind human C3d was demonstrated, indicating that Saimiri is potentially a suitable model for pre-clinical vaccination studies using human C3d-based immunoprotentiation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available