| Summary: | <p>Malaria is a mosquito borne disease caused by parasites of the genus Plasmodium, inflicting a high number of infections and deaths each year. Since the end of the last century incidence rates were reduced significantly, but control measures that facilitated this decrease are starting to fail. An effective vaccine against malaria, particularly one with a marked effect on disease transmission, would undoubtedly be an invaluable tool for control, elimination and finally eradication of this ancient scourge of humankind. Consensus is that a vaccine containing multiple antigens from different life-cycle stages has the most realistic chance of success. Development of an effective malaria vaccine therefore requires two things, identification of critical antigens to be included in the vaccine as well as the assessment of ways to generate multi-antigen vaccines which are effective. During their complex lifecycle, Plasmodium parasites cross host cell membranes multiple times, moving between intracellular and extracellular spaces. The short windows of extracellular location represent the only times parasites are directly exposed to components of the human humoral immunity, making them susceptible to antibody mediated neutralisation. In this thesis I developed and tested novel, antibody inducing vaccines targeting multiple proteins of different life cycle stages with a role in membrane traversal. Furthermore, in an effort to find potential novel antigens suitable for inclusion in a vaccine, I identified a novel protein-protein interaction involved in traversal of the mosquito midgut, a natural bottle neck in the Plasmodium lifecycle. By expanding our understanding of how malaria is spread, as well as demonstrating new strategies to interfere with the process, I hope information from this thesis will aid the development of an effective malaria vaccine.</p>
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