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01.12.2018 | Research | Ausgabe 1/2018 Open Access

Malaria Journal 1/2018

In silico epitope mapping and experimental evaluation of the Merozoite Adhesive Erythrocytic Binding Protein (MAEBL) as a malaria vaccine candidate

Zeitschrift:
Malaria Journal > Ausgabe 1/2018
Autoren:
Pedro Cravo, Renato B. Machado, Juliana A. Leite, Taizy Leda, Rossarin Suwanarusk, Najara Bittencourt, Letusa Albrecht, Carla Judice, Stefanie C. P. Lopes, Marcus V. G. Lacerda, Marcelo U. Ferreira, Irene S. Soares, Yun Shan Goh, Daniel Y. Bargieri, François Nosten, Bruce Russell, Laurent Rénia, Fabio T. M. Costa
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12936-017-2144-x) contains supplementary material, which is available to authorized users.

Abstract

Background

Technical 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.

Results

Detailed 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.

Conclusions

The MAEBL antigen is promising candidate towards the development of a malaria vaccine.
Zusatzmaterial
Additional file 1. MAEBL Oligonucleotide position and sequences. (# The nucleotide positions are based on Plasmodium vivax strain Sal-1 MAEBL sequence (PVX_092975) available at PlasmoDB).
Additional file 2. Predicted MHC class I and II epitopes within the Plasmodium yoelii MAEBL antigen generated from a consensus between different epitope prediction programs.
Additional file 3. Predicted Plasmodium yoelii B-cell epitopes within the putative MAEBL antigen. (Epitopes were generated using BCPRED software. Resulting epitopes were subsequently screened for predicted antigenicity using the VaxiJen resource. BLAST was used to interrogate potential homology between the selected P. yoelii epitopes and the P. falciparum and P. vivax MAEBL antigens).
Additional file 4. Alignment of the M2 MAEBL domain sequences of P. vivax isolates. (M2 MAEBL amino acid sequences of Brazilian isolates harvested from Manaus (PvBM_1524, 1530, 1209), Mâncio Lima (PvBML-6, 5, 12), Acrelândia (PvBA_32A, 20A, 02A) and Thailand isolates (PvT_VKBT-100, VKBT-101, VKTS-39) compared to P. vivax Sal-1 strain. Sequences of Brazilian isolates were deposited in GenBank with accession numbers: KX061004 to KX061012).
Literatur
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