Abstract
BackgroundA highly effective vaccine against Plasmodium falciparum malaria should induce potent, strain transcending immunity that broadly protects against the diverse population of parasites circulating globally. We aimed to identify vaccine candidates that fulfill the criteria.MethodsWe have measured growth inhibitory activity of antibodies raised to a range of antigens to identify those that can efficiently block merozoite invasion for geographically diverse strains of P. falciparum.ResultsThis has shown that the conserved Region III-V, of the P. falciparum erythrocyte-binding antigen (EBA)-175 was able to induce antibodies that potently inhibit merozoite invasion across diverse parasite strains, including those reliant on invasion pathways independent of EBA-175 function. Additionally, the conserved RIII-V domain of EBA-140 also induced antibodies with strong in vitro parasite growth inhibitory activity.ConclusionWe identify an alternative, highly conserved region (RIV-V) of EBA-175, present in all EBA proteins, that is the target of potent, strain transcending neutralizing antibodies, that represents a strong candidate for development as a component in a malaria vaccine.
Highlights
The millennium development goals, set 13 years ago by the United Nations, set a target to halt and begin to reverse the spread of malaria, tuberculosis and HIV by 2015
Clinical grade erythrocyte-binding antigen (EBA)-175 Region II from the 3D7 strain (Fig. 1B lane 3) expressed in Pichia pastoris was kindly provided by Science Applications International Corporation (SAIC)
Having identified evidence for cross-strain immunity arising from Regions III-V (RIII-V), we extended Growth Inhibition Assay (GIA) analysis at a fixed concentration of 1 mg/ml against a panel of 13 independent P. falciparum parasite strains chosen on the basis of their global geographical origin and invasion pathway preference
Summary
The millennium development goals, set 13 years ago by the United Nations, set a target to halt and begin to reverse the spread of malaria, tuberculosis and HIV by 2015. Reaching the goal of malaria elimination, and in the longer term its eradication, will require a highly efficacious vaccine. Immunity that targets the circulating asexual stages of Plasmodium falciparum, the causative agent of the most virulent form of human malaria, is the basis of protection from malaria in endemic settings [2,3,4], indicating that a vaccine targeting this stage of the parasite life cycle could provide immunity in susceptible individuals. One favored strategy towards such a vaccine would be to induce immunity that targets the specific process of erythrocyte entry by the blood stage merozoite [5] preventing the cycles of intracellular parasite growth and multiplication. A highly effective vaccine against Plasmodium falciparum malaria should induce potent, strain transcending immunity that broadly protects against the diverse population of parasites circulating globally. We aimed to identify vaccine candidates that fulfill the criteria
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