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Title: Human immune responses to the C-terminus of the malaria vaccine candidate antigen, the major merozoite surface protein of Plasmodium falciparum (PfMSP1)
Author: Egan, Andrea
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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The major merozoite surface protein of Plasmodium falciparum (PtMSP1) is a malaria vaccine candidate antigen. Monoclonal antibodies (mAb) which bind to disulphide-constrained epitopes of PfMSP119 inhibit parasite growth in vitro and immunisation of animals with recombinant proteins representing this region of the molecule protects animals against challenge infection. In addition, epidemiological data demonstrates that antibody responses to the C-terminus of PfMSP1 are associated with protection against clinical symptoms of malaria. To further evaluate the potential of this antigen as a vaccine candidate, I have measured human immune responses to recombinant proteins representing the C-terminus of PfMSP1. I have found that PfMSP119 is naturally antigenic in individuals living in a malaria endemic area and that antibody is cross-reactive between the two major allelic sequences of PfMSP119. However, some individuals consistently remain nonresponsive to PfMSP119 despite life long exposure. To determine whether this is due to a lack of T cell help, I evaluated T cell responses to PfMSP119 in malaria-exposed adults. T cell responsiveness to PfMSP119 is low and appears to be, in part, due to the disulphide-bonded structure to PfMSP119 which may hinder antigen processing. I have found that antibody responses to PfMSP119 are associated with resistance to clinical malaria in two populations of children actively acquiring immunity to malaria. However, not all antibody-positive children were protected from malaria, suggesting that the fine-specificity of the antibody response may be important in determining its ability to provide protection against clinical malaria. I was able to demonstrate that malaria immune IgG, affinity purified to PfMSP119, inhibits parasite growth in vitro and is equally effective against parasites from either PfMSP1 family. This suggests that if protective antibodies could be induced by vaccination, with either allelic form of the protein, infection by all strains of P. falciparum could be controlled.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available