Medical Biology - Theses
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ItemNaturally acquired humoral responses to Plasmodium vivax and Plasmodium falciparum: identification of antigenic targets to inform rational biomarker and vaccine development( 2016)Malaria is an infectious disease caused by Plasmodium spp. parasites, transmitted by the bite of infected Anopheles mosquitoes. Among the five species that can cause disease in humans, P. falciparum and P. vivax are responsible for the majority of the cases and deaths. Due to increased political commitment and funding, the last decades have experienced a dramatic reduction in the burden of malaria, with several countries now attempting to permanently eliminate this disease. Achieving the goal of malaria elimination would be greatly facilitated by the development of biomarkers that can identify the remaining populations at-risk, as well as an effective vaccine. However, while it is clear that individuals living in endemic areas become gradually protected against malaria disease, the targets and mechanisms underlying the acquisition of natural immunity are complex and still poorly understood, hindering the development of such tools. This thesis aimed to investigate comprehensive panel of P. vivax and P. falciparum proteins as targets of natural immunity in Asia Pacific populations, and how this information can be used to inform rational vaccine and biomarker development. Strong associations of antibody responses to both novel and known P. vivax antigens with protection against clinical malaria were identified, as well as optimal antigenic combinations with predicted protective efficacy above 90%. By comparing humoral responses to P. vivax and P. falciparum, this thesis shows that early immune responses are markers of exposure and thus increased risk, whereas prolonged exposure and higher antibody titers are required to achieved clinical protection. The findings of this study support the development of a highly efficacious multicomponent malaria vaccine, and the use of serology as a surveillance tool.