Abstract
BackgroundTechnical limitations for culturing the human malaria parasite Plasmodium vivax have impaired the discovery of vaccine candidates, challenging the malaria eradication agenda. The immunogenicity of the M2 domain of the Merozoite Adhesive Erythrocytic Binding Protein (MAEBL) antigen cloned from the Plasmodium yoelii murine parasite, has been previously demonstrated.ResultsDetailed epitope mapping of MAEBL through immunoinformatics identified several MHCI, MHCII and B cell epitopes throughout the peptide, with several of these lying in the M2 domain and being conserved between P. vivax, P. yoelii and Plasmodium falciparum, hinting that the M2-MAEBL is pan-reactive. This hypothesis was tested through functional assays, showing that P. yoelii M2-MAEBL antisera are able to recognize and inhibit erythrocyte invasion from both P. falciparum and P. vivax parasites isolated from Thai patients, in ex vivo assays. Moreover, the sequence of the M2-MAEBL is shown to be highly conserved between P. vivax isolates from the Amazon and Thailand, indicating that the MAEBL antigen may constitute a vaccine candidate outwitting strain-specific immunity.ConclusionsThe MAEBL antigen is promising candidate towards the development of a malaria vaccine.
Highlights
Technical limitations for culturing the human malaria parasite Plasmodium vivax have impaired the discovery of vaccine candidates, challenging the malaria eradication agenda
BLAST searches with these epitopes against human malaria parasite sequences revealed that 12 epitopes present homology to both P. falciparum and P. vivax sequences
All but one of these fourteen epitopes lying in the M1 and M2 domains are conserved between P. yoelii, P. vivax and P. falciparum
Summary
Technical limitations for culturing the human malaria parasite Plasmodium vivax have impaired the discovery of vaccine candidates, challenging the malaria eradication agenda. The difficulty to grow P. vivax in vitro for long periods [3] challenges ongoing strategies for identification of novel vaccine candidates against this parasite. Considering these roadblocks, an approach to develop vaccines against P. vivax might rely on the use of malaria antigens conserved amongst species. The immunogenicity of M2 MAEBL (Merozoite Adhesive Erythrocytic Binding Protein) domain of Plasmodium yoelii has been demonstrated. This vaccine candidate conferred 90% protection in immunized mice after lethal challenge and corresponding antisera inhibited significantly erythrocyte invasion by P. yoelii [4].
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