Abstract
Malaria parasite infection is initiated by the mosquito-transmitted sporozoite stage, a highly motile invasive cell that targets hepatocytes in the liver for infection. A promising approach to developing a malaria vaccine is the use of proteins located on the sporozoite surface as antigens to elicit humoral immune responses that prevent the establishment of infection. Very little of the P. falciparum genome has been considered as potential vaccine targets, and candidate vaccines have been almost exclusively based on single antigens, generating the need for novel target identification. The most advanced malaria vaccine to date, RTS,S, a subunit vaccine consisting of a portion of the major surface protein circumsporozoite protein (CSP), conferred limited protection in Phase III trials, falling short of community-established vaccine efficacy goals. In striking contrast to the limited protection seen in current vaccine trials, sterilizing immunity can be achieved by immunization with radiation-attenuated sporozoites, suggesting that more potent protection may be achievable with a multivalent protein vaccine. Here, we provide the most comprehensive analysis to date of proteins located on the surface of or secreted by Plasmodium falciparum salivary gland sporozoites. We used chemical labeling to isolate surface-exposed proteins on sporozoites and identified these proteins by mass spectrometry. We validated several of these targets and also provide evidence that components of the inner membrane complex are in fact surface-exposed and accessible to antibodies in live sporozoites. Finally, our mass spectrometry data provide the first direct evidence that the Plasmodium surface proteins CSP and TRAP are glycosylated in sporozoites, a finding that could impact the selection of vaccine antigens.
Highlights
Malaria remains one of the major global infectious diseases, responsible for nearly 438,000 deaths and 150 to 300 million new infections annually (World Malaria Report 2015, WHO)
Though all clinical symptoms are attributable to the blood stages, it is only by attacking the transmission stages that we can make an impact on the economic and health burdens of malaria
We use state-of-the-art biochemistry tools to identify the proteins on the sporozoite surface and find that two of the most studied proteins, circumsporozoite protein (CSP) and thrombospondin-related anonymous protein (TRAP), have post-translational modifications
Summary
Malaria remains one of the major global infectious diseases, responsible for nearly 438,000 deaths and 150 to 300 million new infections annually (World Malaria Report 2015, WHO). This disease, found in much of the tropical and subtropical regions of the world, is perpetuated through the mosquito-borne transmission of a eukaryotic parasite of the genus Plasmodium. During the blood stage of infection, the iterative cycles of replication lead to high parasite numbers and to all clinical symptoms of malaria. Targeting the asymptomatic sporozoite and liver stage parasites, a time when parasite numbers are low, can lead to elimination of the parasite before it advances to the symptomatic stage of disease
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.
