Chemically Treated Malaria Parasites as a Multimodal System for Vaccine Development
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Current measures to control malaria are becoming unreliable due to the emergence of parasite and vector resistance. Therefore, development of a safe and effective vaccine is essential for the eventual eradication of malaria. Challenges that have hindered malaria vaccine research include antigenic polymorphism, reproducing correlates of protection from preclinical to clinical studies and the paucity of challenge models to test vaccine efficacy. Altering the virulence of the whole parasite using genetic manipulation, irradiation or chemical treatment has been used as an alternative vaccine strategy to address these challenges. A whole parasite vaccine should elicit a potent, protective immune response and overcome the limited efficacy observed in leading subunit vaccine candidates, such as RTS,S. Previous publications from our laboratory have demonstrated that chemically attenuated blood-stage parasites persist in the blood at sub-patent levels. In the P. chabaudi rodent model, CD4+ T cells mediated protection upon homologous and heterologous challenge in an antibody-independent manner. However, in the P. yoelii model, protection was mediated in a cell- and antibody-dependent manner. Prior to testing this approach in humans, a pilot study was done in non-splenectomised Aotus nancymaae monkeys to investigate the persistence and immunogenicity of a single dose of chemically attenuated ring-stage P. falciparum FVO parasites (CAPs). These CAPs induced proliferation of parasite-specific T cells; however, no parasite-specific IgG was detected. These experiments lay the groundwork for assessment of CAPs in humans as a potential vaccine against malaria.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Institute for Glycomics
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Malaria vaccine research