Computational characterization of Plasmodium falciparum proteomic data for screening of potential vaccine candidates

Singh, Satarudra Prakash; Khan, Feroz; Mishra, Bhartendu Nath

doi:10.1016/j.humimm.2009.11.009

Cited by 22 publications

(15 citation statements)

References 45 publications

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“…These prediction data are useful for novel malaria vaccine design because the promiscuous and supertype peptide binders enable the reduction of the number of predicted epitopes without compromising the population coverage. 50,51 Further, it is important to consider whether each MHC binding peptide is being correctly processed from the native antigen and subsequently displayed on the surface of antigenpresenting cells. At present, it is possible to predict the naturally processed peptides using the NetCTL algorithm with a combined epitope prediction score of 0.75, which includes predictions of proteasomal cleavage, TAP binding, and HLA binding.…”

Section: Resultsmentioning

confidence: 99%

Characterization of Plasmodium falciparum Proteome at Asexual Blood Stages for Screening of Effective Vaccine Candidates: An Immunoinformatics Approach

Singh

Verma

Mishra

2015

Immunol Immunogenet Insights

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Malaria is a complex parasitic disease that is currently causing great concerns globally owing to the resistance to antimalarial drugs and lack of an effective vaccine. The present study involves the characterization of extracellular secretory proteins as vaccine candidates derived from proteome analysis of Plasmodium falciparum at asexual blood stages of malaria. Among the screened 32 proteins, 31 were predicted as antigens by the VaxiJen program, and 26 proteins had less than two transmembrane spanning regions predicted using the THMMM program. Moreover, 10 and 5 proteins were predicted to contain secretory signals by SignalP and TargetP, respectively. T-cell epitope prediction using MULTIPRED2 and NetCTL programs revealed that most of the predicted antigens are immunogenic and contain more than 10% supertype and 5% promiscuous epitopes of HLA-A, -B, or -DR. We anticipate that T-cell immune responses against asexual blood stages of Plasmodium are dispersed on a relatively large number of parasite antigens. This is the first report, to the best of our knowledge, offering new insights, at the proteome level, for the putative screening of effective vaccine candidates against the malaria pathogen. The findings also suggest new ways forward for the modern omics-guided vaccine target discovery using reverse vaccinology.

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Section: Resultsmentioning

confidence: 99%

Characterization of Plasmodium falciparum Proteome at Asexual Blood Stages for Screening of Effective Vaccine Candidates: An Immunoinformatics Approach

Singh

Verma

Mishra

2015

Immunol Immunogenet Insights

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“…The subsequent step predicts the presence of immunogenic T cell epitopes in all the 5 GDPAA and 5 RSKMA [35]. These T cell epitopes were further screened by VaxiJen2.0 tool that predicted the antigenic epitopes with threshold ≥ 0.5 [32].…”

Section: Prediction Of T Cell Epitopesmentioning

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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“…P. falciparum has a large genome encoding over 5300 proteins, with stage-specific expression and variation within a single strain [125]. Singh et al [126] used VaxiJen to identify 22 probable antigens, containing up to 15,000 predicted epitopes binding to HLA class I and II supertypes and covering 95% of the human population. The complete proteome of P. falciparum, after excluding human homologs, was subjected to subcellular localization prediction, with outer membrane proteins analyzed by VaxiJen [127].…”

Section: Prediction Of Parasite Immunogensmentioning

confidence: 99%

Immunogenicity Prediction by VaxiJen: A Ten Year Overview

Zaharieva¹,

Димитров²,

Flower³

et al. 2017

J Proteomics Bioinform

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Computational characterization of Plasmodium falciparum proteomic data for screening of potential vaccine candidates

Cited by 22 publications

References 45 publications

Characterization of Plasmodium falciparum Proteome at Asexual Blood Stages for Screening of Effective Vaccine Candidates: An Immunoinformatics Approach

Characterization of Plasmodium falciparum Proteome at Asexual Blood Stages for Screening of Effective Vaccine Candidates: An Immunoinformatics Approach

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

Immunogenicity Prediction by VaxiJen: A Ten Year Overview

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