Abstract
Malaria symptoms and pathology are initiated by invasion of host erythrocytes by Plasmodium merozoites in a complex process that involves interactions between parasite and host erythrocyte proteins. Erythrocyte invasion presents attractive targets for malaria vaccine and drug development. Recently it was observed that antibodies against PfMSA180 (PF3D7_1014100) are associated with protection from symptomatic malaria, suggesting that this protein is a target of naturally acquired protective antibodies. Here we characterize PfMSA180, a ~170 kDa merozoite surface antigen that is potentially involved in erythrocyte invasion. PfMSA180 synthesized by the wheat germ cell-free system was used to raise antibodies in rabbits. Growth inhibition assays revealed that parasite invasion is inhibited by antibodies to the PfMSA180 C-terminal region, which contains an erythrocyte-binding domain. Surface plasmon resonance analysis showed that PfMSA180 specifically interacts with human erythrocyte integrin associated protein (CD47), suggesting that PfMSA180 plays a role during merozoite invasion of erythrocytes. Polymorphism analysis revealed that pfmsa180 is highly conserved among field isolates. We show that naturally acquired PfMSA180-specific antibodies responses are associated with protective immunity in a malaria-exposed Thai population. In sum, the data presented here supports further evaluation of the conserved erythrocyte-binding C-terminal region of PfMSA180 as an asexual blood-stage malaria vaccine candidate.
Highlights
Plasmodium falciparum malaria is a major cause of death in young children and pregnant women in developing and underdeveloped countries[1]
The captured proteins were eluted by either on-column cleavage with AcTEV protease (Thermo Fisher Scientific, Waltham, MA) (Tr1, 2 and 4), targeting a tobacco etch virus (TEV) protease recognition site located between the glutathione S-transferase (GST) tag and the recombinant protein, or with 20 mM glutathione (Tr3 and 5)
While screening for targets of protective immunity in malaria, we observed lower antibody responses against PfMSA180 (PF3D7_1014100) in individuals with symptomatic malaria than those with asymptomatic infection, suggesting that the protein is a target of naturally acquired protective immunity[23]
Summary
Plasmodium falciparum malaria is a major cause of death in young children and pregnant women in developing and underdeveloped countries[1]. Malaria symptoms and pathology are the result of invasion of host erythrocytes by Plasmodium merozoites in a complex series of well-orchestrated molecular events involving interactions of parasite and host erythrocyte proteins[5,6]. This key stage presents an attractive target for vaccine and drug development[7,8]. In this study we describe the functional characterization of PF3D7_1014100 (named merozoite surface antigen 180, PfMSA180) as a P. falciparum merozoite surface protein that is likely involved in erythrocyte invasion. The data presented here shows that PfMSA180 warrants evaluation as a candidate malaria vaccine
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
