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

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Claire Aguttu ◽  
Brenda Apio Okech ◽  
Ambrose Mukisa ◽  
George William Lubega
Keyword(s):  
Plasmodium Falciparum ◽  
Protective Efficacy ◽  
Cell Epitope ◽  
Extracellular Proteins ◽  
Sub Saharan Africa ◽  
Reverse Vaccinology ◽  
Effective Vaccine ◽  
Hypothetical Proteins ◽  
Uncharacterized Protein ◽  
Vaccine Candidates

Abstract 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.

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

2015 ◽  
Vol 7 ◽  
pp. III.S24755 ◽  
Author(s):  
Satarudra Prakash Singh ◽  
Vishal Verma ◽  
Bhartendu Nath Mishra
Keyword(s):  
Plasmodium Falciparum ◽  
T Cell ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Proteome Analysis ◽  
Effective Vaccine ◽  
Secretory Proteins ◽  
Vaccine Candidates ◽  
Proteome Level

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.

scholarly journals Covid-19 vaccine trials and ethics: Protection delayed is protection denied

2020 ◽  
pp. 01-03
Author(s):  
T Jacob John ◽  
Dhanya Dharmapalan
Keyword(s):  
Large Scale ◽  
Protective Efficacy ◽  
Informed Choice ◽  
Effective Vaccine ◽  
Compassionate Use ◽  
Vaccine Research ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Risk Of Death ◽  
Vaccine Trials

Abstract The Covid-19 pandemic is raging, taking a heavy toll of lives and livelihoods. The need for safe and effective vaccine(s) is urgent. Vaccine research has progressed rapidly and a few vaccine candidates have passed trial Phases 1 and 2, confirming reasonable safety and immunogenicity parameters. They are ready for large scale Phase 3 trials to quantify protective efficacy, if any, and to detect uncommon but serious adverse effects, if any. These developments present unprecedented opportunities and challenges, scientific and ethical. Globally hundreds die every day due to Covid-19, and emergency/compassionate use of vaccine candidates that are ready for Phase 3 trials are likely to save lives. We perceive an ethical imperative to allow such vaccination for those at high risk of death who voluntarily make such an informed choice – for them protection delayed will be tantamount to protection denied.

scholarly journals Getting closer to a vaccine against malaria

2011 ◽  
Vol 32 (3) ◽  
pp. 127
Author(s):  
Robin F Anders
Keyword(s):  
Malaria Vaccine ◽  
Protective Efficacy ◽  
Sub Saharan Africa ◽  
Bed Nets ◽  
Effective Vaccine ◽  
Early Case ◽  
Sub Saharan ◽  
Global Eradication ◽  
Effective Use ◽  
Early Case Detection

Despite recent progress in the control of malaria in several countries, this disease still kills nearly one million young children in sub-Saharan Africa each year and it contributes significantly to poverty in many of the poorest countries in the world. The effective use of existing control tools (insecticide-impregnated bed nets, residual insecticide spraying and early case detection with effective treatment) should eliminate malaria from additional regions but global eradication of malaria is not feasible without the development of a highly effective vaccine. The most advanced malaria vaccine, known as RTS,S, is likely to be licensed for use in the next few years. The protective efficacy of RTS,S is unlikely to exceed 50% but numerous other approaches to vaccinating against malaria are showing some promise and, consequently, there are good prospects that a second-generation malaria vaccine will be much more effective.

scholarly journals Preliminary Work Towards Finding Proteins as Potential Vaccine Candidates for Vibrio cholerae Pakistani Isolates through Reverse Vaccinology

Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 195 ◽  
Author(s):  
Samia Zeb ◽  
Amjad Ali ◽  
Sardar Muhammad Gulfam ◽  
Habib Bokhari
Keyword(s):  
Vibrio Cholerae ◽  
Tertiary Structure ◽  
Diarrheal Disease ◽  
Vaccine Development ◽  
Protein A ◽  
Reverse Vaccinology ◽  
Whole Genome Sequence ◽  
Effective Vaccine ◽  
Vaccine Candidates ◽  
Potential Vaccine

Background and Objective: Vibrio cholerae continues to emerge as a dangerous pathogen because of increasing resistance to a number of antibiotics. This paper provides a solution to emerging antibiotic resistance by introducing novel proteins as vaccine candidates against cholera. Materials and Methods: Vibrio cholerae genome versatility is a hurdle for developing a vaccine to combat diarrhoeal infection, so its core gene information was used to determine a potential vaccine candidate. Whole genome sequence data of more than 100 Vibrio cholerae strains were used simultaneously to get core genome information. The VacSol pipeline based on reverse vaccinology was selected to address the problem of safe, cheap, temperature-stable, and effective vaccine candidates which can be used for vaccine development against Vibrio cholerae. VacSol screens vaccine candidates using integrated, well-known, and robust algorithms/tools for proteome analysis. The proteomes of the pathogens were initially screened to predict homology using BLASTp. Proteomes that are non-homologous to humans are then subjected to a predictor for localization. Helicer predicts transmembrane helices for the protein. Proteins failing to comply with the set parameters were filtered at each step, and finally, 11 proteins were filtered as vaccine candidates. Results: This selected group of vaccine candidates consists of proteins from almost all structural parts of Vibrio cholerae. Their blast results show that this filtered group includes flagellin A protein, a protein from the Zn transporter system, a lipocarrier outer membrane protein, a peptidoglycan-associated protein, a DNA-binding protein, a chemotaxis protein, a tRNA Pseuriudine synthase A, and two selected proteins, which were beta lactamases. The last two uncharacterized proteins possess 100% similarity to V. albensis and Enterobacter, respectively. Tertiary structure and active site determination show a large number of pockets on each protein. Conclusions: The most interesting finding of this study is that 10 proteins out of 11 filtered proteins are introduced as novel potential vaccine candidates. These novel vaccine candidates can result in the development of cost-effective and broad-spectrum vaccines which can be used in countries where cholera is a major contributor to diarrheal disease.

Identification of potential vaccine candidates against SARS-CoV-2, A step forward to fight COVID 19: A Reverse Vaccinology Approach (Preprint)

2021 ◽  
Author(s):  
Ekta Gupta ◽  
Rupesh Kumar Mishra ◽  
Ravi Ranjan Kumar Niraj
Keyword(s):  
Viral Disease ◽  
Surface Glycoprotein ◽  
Antigenic Peptide ◽  
Reverse Vaccinology ◽  
Effective Vaccine ◽  
Global Public Health ◽  
Health Crisis ◽  
Vaccine Candidates ◽  
Cell Mediated Immune Response ◽  
Potential Vaccine

UNSTRUCTURED The recent Coronavirus Disease 2019 (COVID-19) causes an immense health crisis to global public health. The etiological agent of COVID-19, a recently arose disease is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Presently, more research in the field of effecting vaccine against this emerged viral disease is indeed a need of the hour. In the current study, we collected SARS-CoV-2 genome which is prominent in India against human host, furthermore using reverse vaccinology here we prove effective vaccine candidates that can be milestone in the battle against COVID19. This novel study divulged one promising antigenic peptide GVYFASTEK from surface glycoprotein (protein accession no. - QIA98583.1) of SARS-CoV-2, which was predicted to be interacted with MHC alleles and showed up to 90% conservancy and high value of antigenicity. Subsequently, the molecular docking and simulation studies were verified molecular interaction of this prime antigenic peptide with the residues of HLA-A*11-01 allele for MHC Class I. After vigorous analysis, this peptide was predicted to be a suitable epitope that is capable to induce a strong cell-mediated immune response against the SARS-CoV-2. Consequences from the current study could facilitate selecting SARS-CoV-2 epitopes for vaccine production pipelines in the immediate future. This novel research will certainly pave the way for a fast, reliable and virtuous platform to provide timely countermeasure of this dangerous pandemic disease, COVID-19.

scholarly journals Vaccinomics driven proteome-wide screening of Haemophilus influenzae for the prediction of common putative vaccine candidates

2021 ◽  
Author(s):  
Naseeha Bibi ◽  
Najam-us-Sahar Sadaf Zaidi ◽  
Muhammad Tahir ◽  
Mustafeez Mujtaba Babar
Keyword(s):  
Haemophilus Influenzae ◽  
Protein Interactions ◽  
Protein Structures ◽  
Cell Epitope ◽  
Genomic Analysis ◽  
Effective Vaccine ◽  
Comparative Genomic ◽  
Vaccine Candidates ◽  
Invasive Infections ◽  
Different Strains

Haemophilus influenzae colonizes the respiratory tract and is associated with life-threatening invasive infections. The recent rise in its global prevalence, even in the presence of multiple vaccines, indicate an urgent need for developing cross-strain effective vaccine strategies. Our work focused on identifying the universally conserved antigenic regions of H. influenzae that can be used for developing new vaccines. A variety of bioinformatics tools were applied for the comprehensive geno-proteomic analysis of H. influenzae type “a” strain, as reference serotype, through which subcellular localization, essentiality, virulence, and non-host homology were determined. B and T-Cell epitope mapping of 3D protein structures were performed. Thereafter, molecular docking with HLA DRB1*0101 and comparative genome analysis established the candidature of identified regions. Based on the established vaccinomics criteria, five target proteins were predicted as novel vaccine candidates. Among these, 9 epitopic regions were identified that could regulate the lymphocyte activity through strong protein-protein interactions. Comparative genomic analysis exhibited that the identified regions were highly conserved among the different strains of H. influenzae. Based on multiple immunogenic factors, the five prioritized proteins and their predicted epitopes were identified as the ideal common putative vaccine candidate against typeable strains.

scholarly journals A T-Cell Epitope-Based Multi-Epitope Vaccine Designed Using Human HLA Specific T Cell Epitopes Induces a Near-Sterile Immunity against Experimental Visceral Leishmaniasis in Hamsters

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1058
Author(s):  
Aryandra Arya ◽  
Sunil K. Arora
Keyword(s):  
T Cell ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Cell Epitope ◽  
Effective Vaccine ◽  
T Cell Epitope ◽  
Hamster Model ◽  
Vaccine Candidates

Visceral leishmaniasis is a neglected tropical disease affecting 12 million people annually. Even in the second decade of the 21st century, it has remained without an effective vaccine for human use. In the current study, we designed three multiepitope vaccine candidates by the selection of multiple IFN-γ inducing MHC-I and MHC-II binder T-cell specific epitopes from three previously identified antigen genes of Leishmania donovani from our lab by an immuno-informatic approach using IFNepitope, the Immune Epitope Database (IEDB) T cell epitope identification tools, NET-MHC-1, and NET MHC-2 webservers. We tested the protective potential of these three multiepitope proteins as a vaccine in a hamster model of visceral leishmaniasis. The immunization data revealed that the vaccine candidates induced a very high level of Th1 biased protective immune response in-vivo in a hamster model of experimental visceral leishmaniasis, with one of the candidates inducing a near-sterile immunity. The vaccinated animals displayed highly activated monocyte macrophages with the capability of clearing intracellular parasites due to increased respiratory burst. Additionally, these proteins induced activation of polyfunctional T cells secreting INF-γ, TNF-α, and IL-2 in an ex-vivo stimulation of human peripheral blood mononuclear cells, further supporting the protective nature of the designed candidates.

scholarly journals Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Kara A. Moser ◽  
Elliott F. Drábek ◽  
Ankit Dwivedi ◽  
Emily M. Stucke ◽  
Jonathan Crabtree ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Vaccine Efficacy ◽  
De Novo ◽  
Genome Structure ◽  
Geographic Origin ◽  
Cell Epitope ◽  
Sub Saharan Africa ◽  
Clinical Isolates ◽  
Sub Saharan ◽  
Sequencing Platforms

Abstract Background Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable protection against homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation of these results and understanding of their relevance to vaccine efficacy have been hampered by the lack of knowledge on genetic differences between vaccine and CHMI strains, and how these strains are related to parasites in malaria endemic regions. Methods Whole genome sequencing using long-read (Pacific Biosciences) and short-read (Illumina) sequencing platforms was conducted to generate de novo genome assemblies for the vaccine strain, NF54, and for strains used in heterologous CHMI (7G8 from Brazil, NF166.C8 from Guinea, and NF135.C10 from Cambodia). The assemblies were used to characterize sequences in each strain relative to the reference 3D7 (a clone of NF54) genome. Strains were compared to each other and to a collection of clinical isolates (sequenced as part of this study or from public repositories) from South America, sub-Saharan Africa, and Southeast Asia. Results While few variants were detected between 3D7 and NF54, we identified tens of thousands of variants between NF54 and the three heterologous strains. These variants include SNPs, indels, and small structural variants that fall in regulatory and immunologically important regions, including transcription factors (such as PfAP2-L and PfAP2-G) and pre-erythrocytic antigens that may be key for sporozoite vaccine-induced protection. Additionally, these variants directly contributed to diversity in immunologically important regions of the genomes as detected through in silico CD8+ T cell epitope predictions. Of all heterologous strains, NF135.C10 had the highest number of unique predicted epitope sequences when compared to NF54. Comparison to global clinical isolates revealed that these four strains are representative of their geographic origin despite long-term culture adaptation; of note, NF135.C10 is from an admixed population, and not part of recently formed subpopulations resistant to artemisinin-based therapies present in the Greater Mekong Sub-region. Conclusions These results will assist in the interpretation of vaccine efficacy of whole-organism vaccines against homologous and heterologous CHMI.

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