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

Singh, Satarudra Prakash; Verma, Vishal; Mishra, Bhartendu Nath

doi:10.4137/iii.s24755

Cited by 8 publications

(5 citation statements)

References 67 publications

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“…The present strategy is similar to the reverse vaccinology approach adopted by John et al [ 28 ], for identifying common vaccine candidates from L. major and L. infantum genomes. Additionally, Singh et al [ 29 , 30 ] also utilized the similar approach of MHC supertype based epitope identification, as a strategy to mine proteomic data for identification of novel CTL epitopes, in Plasmodium falciparum .…”

Section: Resultsmentioning

confidence: 99%

Genome-Wide Prediction of Vaccine Candidates forLeishmania major: An Integrated Approach

Singh

Roopendra

Mishra

2015

Journal of Tropical Medicine

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Despite the wealth of information regarding genetics of the causative parasite and experimental immunology of the cutaneous leishmaniasis, there is currently no licensed vaccine against it. In the current study, a two-level data mining strategy was employed, to screen the Leishmania major genome for promising vaccine candidates. First, we screened a set of 25 potential antigens from 8312 protein coding sequences, based on presence of signal peptides, GPI anchors, and consensus antigenicity predictions. Second, we conducted a comprehensive immunogenic analysis of the 25 antigens based on epitopes predicted by NetCTL tool. Interestingly, results revealed that candidate antigen number 1 (LmjF.03.0550) had greater number of potential T cell epitopes, as compared to five well-characterized control antigens (CSP-Plasmodium falciparum, M1 and NP-Influenza A virus, core protein-Hepatitis B virus, and PSTA1-Mycobacterium tuberculosis). In order to determine an optimal set of epitopes among the highest scoring predicted epitopes, the OptiTope tool was employed for populations susceptible to cutaneous leishmaniasis. The epitope (127SLWSLLAGV) from antigen number 1, found to bind with the most prevalent allele HLA-A⁎0201 (25% frequency in Southwest Asia), was predicted as most immunogenic for all the target populations. Thus, our study reasserts the potential of genome-wide screening of pathogen antigens and epitopes, for identification of promising vaccine candidates.

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Section: Resultsmentioning

confidence: 99%

Genome-Wide Prediction of Vaccine Candidates forLeishmania major: An Integrated Approach

Singh

Roopendra

Mishra

2015

Journal of Tropical Medicine

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“…Two groups of HPs exist: uncharacterized protein families and domains of unknown function. Many studies have identified and characterized hypothetical proteins from different microorganisms which appear to be of great importance [16][17][18][19][20][21]. Reverse vaccinology (RV) is a new approach to identify drug target and vaccine candidates without the need for culturing the parasite [22].…”

Section: Introductionmentioning

confidence: 99%

Screening and characterization of hypothetical proteins of Plasmodium falciparum as novel vaccine candidates in the fight against malaria using reverse vaccinology

Aguttu

Okech

Mukisa

et al. 2021

Journal of Genetic Engineering and Biotechnology

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Background Plasmodium falciparum is the most deadly and leading cause of morbidity and mortality in Africa. About 90% of all malaria deaths in the world today occur in Sub-Saharan Africa especially in children aged < 5 years. In 2018, it was reported that there were 228 million malaria cases that resulted in 405,000 deaths from 91 countries. Currently, a fully effective and long-lasting preventive malaria vaccine is still elusive therefore more effort is needed to identify better effective vaccine candidates. The aim of this study was to identify and characterize hypothetical proteins as vaccine candidates derived from Plasmodium falciparum 3D7 genome by reverse vaccinology. Results Of the 23 selected hypothetical proteins, 5 were predicted on the extracellular localization by WoLFPSORTv.2.0 program and all the 5 had less than 2 transmembrane regions that were predicted by TMHMMv2.0 and HMMTOP programs at default settings. Two out of the five proteins lacked secretory signal peptides as predicted by SignalP program. Among the 5 extracellular proteins, 3 were predicted to be antigenic by VaxiJen (score ≥ 0.5) and had negative GRAVY values ranging from − 1.156 to − 0.440. B cell epitope prediction by ABCpred and BCpred programs revealed a total of 15 antigenic epitopes. A total of 13 cytotoxic T cells were predicted from the 3 proteins using CTLPred online server. Only 2 out of the 13 CTL were antigenic, immunogenic, non-allergenic, and non-toxic using VaxiJen, IEDB, AllergenFp, and Toxinpred servers respectively in that order. Five HTL peptides from XP_001351030.1 protein are predicted inducers of all the three cytokines. STRING protein–protein network analysis of HPs revealed XP_001350955.1 closely interacts with nucleoside diphosphate kinase (PF13-0349) at 0.704, XP_001351030.1 interacts with male development protein1 (Mdv-1) at 0.645, and XP_001351047.1 with an uncharacterized protein (MAL8P1.53) at 0.400. Conclusion Reverse vaccinology is a promising strategy for the screening and identification of antigenic antigens with potential capacity to elicit cellular and humoral immune responses against P. falciparum infection. In this study, potential vaccine candidates of Plasmodium falciparum were identified and screened using standard bioinformatics tools. The vaccine candidates contained antigenic and immunogenic epitopes which could be considered for novel and effective vaccine targets. However, we strongly recommend in vivo and in vitro experiments to validate their immunogenicity and protective efficacy to completely decipher the vaccine targets against malaria.

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“…Although, there are more than 30 vaccine candidates of malaria that were involved in different clinical phase trail, but they did not make a globally effective vaccine [5,6]. The RTS,S is latest leading vaccine candidate with partial protection efficacy (39.0% in clinical malaria and 20.5% in severe malaria case) and restricted in limited regions of African countries [7].…”

Section: Introductionmentioning

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

Cited by 8 publications

References 67 publications

Genome-Wide Prediction of Vaccine Candidates forLeishmania major: An Integrated Approach

Genome-Wide Prediction of Vaccine Candidates forLeishmania major: An Integrated Approach

Screening and characterization of hypothetical proteins of Plasmodium falciparum as novel vaccine candidates in the fight against malaria using reverse vaccinology

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

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