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

Cravo, Pedro Vitor Lemos; Machado, Renato; Leite, Juliana Almeida; Leda, Taizy; Suwanarusk, Rossarin; Bittencourt, Najara; Albrecht, Letusa; Judice, Carla C.; Lopes, Stefanie Costa Pinto; Lacerda, Marcus; Ferreira, Marcelo U.; Soares, Irene S.; Goh, Yun Shan; Bargieri, Daniel Youssef; Nosten, François; Russell, Bruce; Rénia, Laurent; Costa, Fabio T. M.

doi:10.1186/s12936-017-2144-x

Cited by 6 publications

(5 citation statements)

References 38 publications

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“…However, a better understanding of the interactions between the ZIKV and DENV immunity, such as induction by vaccination or by natural infection, will be necessary to provide safe and efficient vaccines [115]. Several studies have reported how the computational prediction of antigenic peptides were successfully validated experimentally to combat HIV-1, malaria parasites and leishmaniasis, a vector-borne parasitic disease [116,117,118]. In validating the predicted epitopes, it is suggested to integrate genomics with proteomics approaches to represent a valid strategy in refining the antigen characterizations as well as give the useful insights on abundance and subcellular localization of pathogenic antigens [119].…”

Section: Discussionmentioning

confidence: 99%

Peptide-Based Subunit Vaccine Design of T- and B-Cells Multi-Epitopes against Zika Virus Using Immunoinformatics Approaches

et al. 2019

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The Zika virus disease, also known as Zika fever is an arboviral disease that became epidemic in the Pacific Islands and had spread to 18 territories of the Americas in 2016. Zika virus disease has been linked to several health problems such as microcephaly and the Guillain–Barré syndrome, but to date, there has been no vaccine available for Zika. Problems related to the development of a vaccine include the vaccination target, which covers pregnant women and children, and the antibody dependent enhancement (ADE), which can be caused by non-neutralizing antibodies. The peptide vaccine was chosen as a focus of this study as a safer platform to develop the Zika vaccine. In this study, a collection of Zika proteomes was used to find the best candidates for T- and B-cell epitopes using the immunoinformatics approach. The most promising T-cell epitopes were mapped using the selected human leukocyte antigen (HLA) alleles, and further molecular docking and dynamics studies showed a good peptide-HLA interaction for the best major histocompatibility complex-II (MHC-II) epitope. The most promising B-cell epitopes include four linear peptides predicted to be cross-reactive with T-cells, and conformational epitopes from two proteins accessible by antibodies in their native biological assembly. It is believed that the use of immunoinformatics methods is a promising strategy against the Zika viral infection in designing an efficacious multiepitope vaccine.

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Section: Discussionmentioning

confidence: 99%

Peptide-Based Subunit Vaccine Design of T- and B-Cells Multi-Epitopes against Zika Virus Using Immunoinformatics Approaches

et al. 2019

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“…Therefore, these GPI-anchored surface proteins were screened as malarial adhesins and adhesin-like proteins by MAAP tool [ 24 – 26 ]. The VaxiJen2.0 program was used for the evaluation of antigenicity of the malarial adhesins protein sequence [ 27 , 28 ]. Furthermore, to assess the potential impact of membrane proximity, transmembrane regions of potential antigens (pathogenesis-related secretome of P. falciparum ) were predicted using TMHMM2.0 tool [ 29 – 31 ].…”

Section: Methodsmentioning

confidence: 99%

Exploitation of reverse vaccinology and immunoinformatics as promising platform for genome-wide screening of new effective vaccine candidates against Plasmodium falciparum

et al. 2019

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Background: In the current scenario, designing of world-wide effective malaria vaccine against Plasmodium falciparum remain challenging despite the significant progress has been made in last few decades. Conventional vaccinology (isolate, inactivate and inject) approaches are time consuming, laborious and expensive; therefore, the use of computational vaccinology tools are imperative, which can facilitate the design of new and promising vaccine candidates. Results: In current investigation, initially 5548 proteins of P. falciparum genome were carefully chosen for the incidence of signal peptide/ anchor using SignalP4.0 tool that resulted into 640 surface linked proteins (SLP). Out of these SLP, only 17 were predicted to contain GPI-anchors using PredGPI tool in which further 5 proteins were considered as malarial antigenic adhesins by MAAP and VaxiJen programs, respectively. In the subsequent step, T cell epitopes of 5 genome derived predicted antigenic adhesins (GDPAA) and 5 randomly selected known malarial adhesins (RSKMA) were analysed employing MHC class I and II tools of IEDB analysis resource. Finally, VaxiJen scored T cell epitopes from each antigen were considered for prediction of population coverage (PPC) analysis in the world-wide population including malaria endemic regions. The validation of the present in silico strategy was carried out by comparing the PPC of combined (MHC class I and II) predicted epitope ensemble among GDPAA (99.97%), RSKMA (99.90%) and experimentally known epitopes (EKE) of P. falciparum (97.72%) pertaining to world-wide human population. Conclusions:The present study systematically screened 5 potential protective antigens from P. falciparum genome using bioinformatics tools. Interestingly, these GDPAA, RSKMA and EKE of P. falciparum epitope ensembles forecasted to contain highly promiscuous T cell epitopes, which are potentially effective for most of the world-wide human population with malaria endemic regions. Therefore, these epitope ensembles could be considered in near future for novel and significantly effective vaccine candidate against malaria.

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“…MAEBL is a membrane protein of the erythrocyte binding protein (EBL) family. It is expressed in preerythrocytes, blood stage, and salivary glands ( 31 ). Immunoinformatic analysis showed that MAEBL antigens could be promising interspecies and inter strain malaria candidates since they have several conserved epitopes among P. yoelli , P. falciparum and P. vivax ( 31 ).…”

Section: Multistage Vaccinementioning

confidence: 99%

“…It is expressed in preerythrocytes, blood stage, and salivary glands ( 31 ). Immunoinformatic analysis showed that MAEBL antigens could be promising interspecies and inter strain malaria candidates since they have several conserved epitopes among P. yoelli , P. falciparum and P. vivax ( 31 ). Functional studies showed that antibodies against PyMAEBL-M2 were reactive against P. falciparum and P. vivax with significant inhibition of erythrocyte invasion of these parasites ( 31 ).…”

Section: Multistage Vaccinementioning

confidence: 99%

“…To date, it has not been possible to establish P. vivax long-term in vitro culture, which makes antigen discovery more challenging. Thus, some studies seek to identify parasite proteins in silico, whereas features such as antigenicity and immunogenicity are evaluated, and antigens against different stages of the paras'te's life cycle combined with different adjuvants and immunization schedules have been tested (30)(31)(32)(33). These vaccine candidates are categorized as preerythrocytic stage vaccines, blood-stage vaccines, and transmission-blocking vaccines (34).…”

Section: Introductionmentioning

confidence: 99%

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Plasmodium vivax vaccine: What is the best way to go?

Veiga

Moriggi²,

Vettorazzi³

et al. 2023

Front. Immunol.

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Malaria is one of the most devastating human infectious diseases caused by Plasmodium spp. parasites. A search for an effective and safe vaccine is the main challenge for its eradication. Plasmodium vivax is the second most prevalent Plasmodium species and the most geographically distributed parasite and has been neglected for decades. This has a massive gap in knowledge and consequently in the development of vaccines. The most significant difficulties in obtaining a vaccine against P. vivax are the high genetic diversity and the extremely complex life cycle. Due to its complexity, studies have evaluated P. vivax antigens from different stages as potential targets for an effective vaccine. Therefore, the main vaccine candidates are grouped into preerythrocytic stage vaccines, blood-stage vaccines, and transmission-blocking vaccines. This review aims to support future investigations by presenting the main findings of vivax malaria vaccines to date. There are only a few P. vivax vaccines in clinical trials, and thus far, the best protective efficacy was a vaccine formulated with synthetic peptide from a circumsporozoite protein and Montanide ISA-51 as an adjuvant with 54.5% efficacy in a phase IIa study. In addition, the majority of P. vivax antigen candidates are polymorphic, induce strain-specific and heterogeneous immunity and provide only partial protection. Nevertheless, immunization with recombinant proteins and multiantigen vaccines have shown promising results and have emerged as excellent strategies. However, more studies are necessary to assess the ideal vaccine combination and test it in clinical trials. Developing a safe and effective vaccine against vivax malaria is essential for controlling and eliminating the disease. Therefore, it is necessary to determine what is already known to propose and identify new candidates.

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

Cited by 6 publications

References 38 publications

Peptide-Based Subunit Vaccine Design of T- and B-Cells Multi-Epitopes against Zika Virus Using Immunoinformatics Approaches

Peptide-Based Subunit Vaccine Design of T- and B-Cells Multi-Epitopes against Zika Virus Using Immunoinformatics Approaches

Exploitation of reverse vaccinology and immunoinformatics as promising platform for genome-wide screening of new effective vaccine candidates against Plasmodium falciparum

Plasmodium vivax vaccine: What is the best way to go?

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