scholarly journals In Silico Modeling and Immunoinformatics Probing Disclose the Epitope Based PeptideVaccine Against Zika Virus Envelope Glycoprotein

2014 ◽  
Vol 2 (04) ◽  
pp. 44-57 ◽  
Author(s):  
Daga Dadjo Florian ◽  
Mohammad Mahfuz Ali Khan Shawan ◽  
Hafij Al Mahmud ◽  
Md. Mahmudul Hasan ◽  
Afroza Parvin ◽  
...  

Zika virus (ZIKV) is an aedes mosquito borne pathogen belonging to the member of flaviviridae subgroup is the causative agent of an emerging disease called Zika fever, known as a benign infection usually presenting as influenza like illness with cutaneous rash. Due to recent epidemic outbreaks it is realized as a major health risk which need enhanced surveillance, but no attempt has been made to design an epitope based peptide vaccine against Zika virus. Viral envelope proteins are derived from host cell membrane proteins with some viral glycoproteins and are used to cover their protective protein capsid, help the viruses to enter host cells and help them to avoid the host immune response. In this study, amino acid sequence of ZIKV envelope glycoprotein was obtained from a protein database and examined with in silico approaches to determine the most immunogenic epitopes for B cell and T cell which could induce humoral as well as cell mediated immune response. Both the linear and conformational epitopes for B cell were predicted by immunoinformatics tools housed in IEDB resources. The peptide sequence DAHAKRQTVVVLGSQEGAV from position 121 and peptide sequence from 117-137 amino acids were predicted as most potential B cell linear and conformational epitopes respectively. Epitopes for CD4+ and CD8+ T cell were also predicted by using tools within IEDB resource and peptide sequence MMLELDPPF from position 250-258 amino acids was predicted as most immunogenic CD8+ T cell epitope with immune response evoking ability prediction score (I pMHC) of 0.09139 and conservancy of 52.17%. The innate immune response for ZIKV envelope glycoprotein was determined by interferon (IFN)-gamma effectuation and mimicking capacity by immunoinformatics and molecular docking study respectively. However, this is an introductory approach to design an epitope based peptide vaccine against Zika virus; we hope this model will be very much helpful in designing and predicting novel vaccine candidate.

2013 ◽  
Vol 7 ◽  
pp. BBI.S13402 ◽  
Author(s):  
Anayet Hasan ◽  
Mehjabeen Hossain ◽  
Jibran Alam

Saint Louis encephalitis virus, a member of the flaviviridae subgroup, is a culex mosquito-borne pathogen. Despite severe epidemic outbreaks on several occasions, not much progress has been made with regard to an epitope-based vaccine designed for Saint Louis encephalitis virus. The envelope proteins were collected from a protein database and analyzed with an in silico tool to identify the most immunogenic protein. The protein was then verified through several parameters to predict the T-cell and B-cell epitopes. Both T-cell and B-cell immunity were assessed to determine that the protein can induce humoral as well as cell-mediated immunity. The peptide sequence from 330–336 amino acids and the sequence REYCYEATL from the position 57 were found as the most potential B-cell and T-cell epitopes, respectively. Furthermore, as an RNA virus, one important thing was to establish the epitope as a conserved one; this was also done by in silico tools, showing 63.51% conservancy. The epitope was further tested for binding against the HLA molecule by computational docking techniques to verify the binding cleft epitope interaction. However, this is a preliminary study of designing an epitope-based peptide vaccine against Saint Louis encephalitis virus; the results awaits validation by in vitro and in vivo experiments.


Author(s):  
Prekshi Garg ◽  
Neha Srivastava ◽  
Prachi Srivastava

SARS-CoV-2 has been the talk of the town ever since the beginning of 2020. The pandemic has brought the complete world on a halt. Every country is trying all possible steps to combat the disease ranging from shutting the complete economy of the country to repurposing of drugs and vaccine development. The rapid data analysis and widespread tools, software and databases have made bioinformatics capable of giving new insights to the researchers to deal with the current scenario more efficiently. Vaccinomics, the new emerging field of bioinformatics uses concepts of immunogenetics and immunogenomics with in silico tools to give promising results for wet lab experiments. This approach is highly validated for the designing and development of potent vaccines. The present in-silico study was attempted to identify peptide fragments from spike surface glycoprotein that can be efficiently used for the designing and development of epitope-based vaccine designing approach. Both B-cell and T-cell epitopes are predicted using integrated computational tools. VaxiJen server was used for prediction of protective antigenicity of the protein. NetCTL was studied for analyzing most potent T cell epitopes and its subsequent MHC-I interaction through tools provided by IEDB. 3D structure prediction of peptides and MHC-I alleles (HLA-C*03:03) was further done to carry out docking studies using AutoDock4.0. Various tools from IEDB were used to predict B-cell epitopes on the basis of different essential parameters like surface accessibility, beta turns and many more. Based on results interpretation, the peptide sequence from 1138-1145 amino acid and sequence WTAGAAAYY and YDPLQPEL were obtained as a potential B-cell epitope and T-cell epitope respectively. This in-silico study will help us to identify novel epitope-based peptide vaccine target in spike protein of SARS-CoV-2. Further, in-vitro and in-vivo study needed to validate the findings.


Author(s):  
Md Tangigul Haque ◽  
Md Nur Ahad Shah ◽  
Shatabdi Paul ◽  
Md Kawsar Khan ◽  
Payal Barua

AbstractZika virus (ZIKV), a mosquito-borne flavivirus, is now an emerging global public health concern. Currently, the pathogenicity, genetic diversity and the consequences of ZIKV infection are little known but a protective vaccine against ZIKV is an urgency. In this study, we have taken an immunoinformatics based approach to predict epitope cluster region in the whole proteome (3423 amino acids) of ZIKV. We have operated a range of bioinformatics algorithms to determine the epitopes of CD8+ cytotoxic T-cell (CTL), CD4+ helper T-cell (THL) and B cell. We have predicted an epitope cluster of 23 contiguous amino acids (region 1989-2011, WLEARMLLDNIYLQDGLIASLYR) residing on the protein NS3 helicase in ZIKV proteome. This epitope cluster contains fourteen CD4+ (THL) epitopes and six CD8+ (CTL) epitopes. The cluster region predicted to provide 93.86% population coverage worldwide. Finally, we have validated the epitopes by analysing their binding efficiency (binding energy within −4.7 to −6.9 kcal/mol) with specific HLA alleles. Based on our immunoinformatics analysis, we propose the peptide WLEARMLLDNIYLQDGLIASLYR as a new peptide vaccine candidate against Zika virus for further validation.


Coronaviruses ◽  
2021 ◽  
Vol 02 ◽  
Author(s):  
Prekshi Garg ◽  
Neha Srivastava ◽  
Prachi Srivastava

Background: SARS-CoV-2 has been the talk of the town ever since the beginning of 2020. Every country is trying all possible steps to combat the disease ranging from shutting the complete economy of the country to the repurposing of drugs and vaccine development. The rapid data analysis and widespread tools have made bioinformatics capable of giving new insights to deal with the current scenario more efficiently through an emerging field, Vaccinomics. Objective: The present in-silico study was attempted to identify peptide fragments from spike surface glycoprotein of SARS-CoV-2 that can be efficiently used for the development of an epitope-based vaccine designing approach. Methodology: The epitopes of B and T-cell are predicted using integrated computational tools. VaxiJen server, NetCTL, and IEDB tools were used to study, analyze, and predict potent T-cell epitopes, its subsequent MHC-I interactions, and B-cell epitopes. The 3D structure prediction of peptides and MHC-I alleles (HLA-C*03:03) was further done using AutoDock4.0. Result: Based on result interpretation, the peptide sequence from 1138-1145 amino acid and sequence WTAGAAAYY and YDPLQPEL were obtained as potential B-cell and T-cell epitopes respectively. Conclusion: The peptide sequence WTAGAAAYY and the amino acid sequence from 1138-1145 of the spike protein of SARS-CoV-2 can be used as a probable B-cell epitope candidate. Also, the amino acid sequence YDPLQPEL can be used as a potent T-cell epitope. This in-silico study will help us to identify novel epitope-based peptide vaccine targets in the spike protein of SARS-CoV-2. Further, the in-vitro and in-vivo study needed to validate the findings.


PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252052
Author(s):  
Hyung Suk Kim ◽  
Min Gyu Kim ◽  
Kyueng-Whan Min ◽  
Un Suk Jung ◽  
Dong-Hoon Kim

Matrix metalloproteinase-11 (MMP-11) promote cancer invasion and metastasis through degrading the extracellular matrix. Protein degradation by MMP-11 in tumor cells may progressively suppress cancer surveillance activities with blocking immune response in breast cancer. The aim of study is to analyze clinicopathological parameters, molecular interactions and anticancer immune response in patients with MMP-11 expression and to provide candidate target drugs. We investigated the clinicopathologic parameters, specific gene sets, tumor antigenicity, and immunologic relevance according to MMP-11 expression in 226 and 776 breast cancer patients from the Hanyang University Guri Hospital (HUGH) cohort and The Cancer Genome Atlas (TCGA) data, respectively. We analyzed pathway networks and in vitro drug response. High MMP-11 expression was associated with worse survival rate in breast cancer from HUGH cohort and TCGA data (all p < 0.05). In analysis of immunologic gene sets, high MMP-11 expression was related to low immune response such as CD8+T cell, CD4+T cell and B cell. In silico cytometry, there was a decrease of cancer testis antigen and low tumor infiltrating lymphocyte in patient with high MMP-11 expression: activated dendritic cell, CD8+T cell, CD4+ memory T cell, and memory B cell. In pathway networks, MMP-11 was linked to the pathways including low immune response, response to growth hormone and catabolic process. We found that pictilisib and AZ960 effectively inhibited the breast cancer cell lines with high MMP-11 expression. Strategies making use of MMP-11-related hub genes could contribute to better clinical management/research for patients with breast cancer.


1999 ◽  
Vol 73 (2) ◽  
pp. 1205-1212 ◽  
Author(s):  
Kenneth G. Hadlock ◽  
Judy Rowe ◽  
Steven K. H. Foung

ABSTRACT Individuals infected with human T-cell lymphotropic virus type 1 (HTLV-1) develop a robust immune response to the surface envelope glycoprotein gp46 that is partially protective. The relative contribution of antibodies to conformation-dependent epitopes, including those mediating virus neutralization as part of the humoral immune response, is not well defined. We assess in this report the relationship between defined linear and conformational epitopes and the antibodies elicited to these domains. First, five monoclonal antibodies to linear epitopes within gp46 were evaluated for their ability to abrogate binding of three human monoclonal antibodies that inhibit HTLV-1-mediated syncytia formation and recognize conformational epitopes. Binding of antibodies to conformational epitopes was unaffected by antibodies to linear epitopes throughout the carboxy-terminal half and central domain of HTLV-1 gp46. Second, an enzyme-linked immunoadsorbent assay was developed and used to measure serum antibodies to native and denatured gp46 from HTLV-1-infected individuals. In sera from infected individuals, reactivity to denatured gp46 had an average of 15% of the reactivity observed to native gp46. Third, serum antibodies from 24 of 25 of HTLV-1-infected individuals inhibited binding of a neutralizing human monoclonal antibody, PRH-7A, to a conformational epitope on gp46 that is common to HTLV-1 and -2. Thus, antibodies to conformational epitopes comprise the majority of the immune response to HTLV-1 gp46, and the epitopes recognized by these antibodies do not appear to involve sequences in previously described immunodominant linear epitopes.


Author(s):  
Wahiba Ezzemani ◽  
Marc P. Windisch ◽  
Anass Kettani ◽  
Haya Altawalah ◽  
Jalal Nourlil ◽  
...  

Background: Globally, the recent outbreak of Zika virus (ZIKV) in Brazil, Asia Pacific, and other countries highlighted the unmet medical needs. Currently, there are neither effective vaccines nor therapeutics available to prevent or treat ZIKV infection. Objective: In this study, we aimed to design an epitope-based vaccine for ZIKV using an in silico approach to predict and analyze B- and T-cell epitopes. Methods: The prediction of the most antigenic epitopes has targeted the capsid and the envelope proteins as well as nonstructural proteins NS5 and NS3 using immune-informatics tools PROTPARAM, CFSSP, PSIPRED, and Vaxijen v2.0. B and T-cell epitopes were predicted using ABCpred, IEDB, TepiTool, and their toxicity were evaluated using ToxinPred. The 3-dimensional epitope structures were generated by PEP-FOLD. Energy minimization was performed using Swiss-Pdb Viewer, and molecular docking was conducted using PatchDock and FireDock server. Results: As a result, we predicted 307 epitopes of MHCI (major histocompatibility complex class I) and 102 epitopes of MHCII (major histocompatibility complex class II). Based on immunogenicity and antigenicity scores, we identified the four most antigenic MHC I epitopes: MVLAILAFLR (HLA-A*68 :01), ETLHGTVTV (HLA-A*68 :02), DENHPYRTW (HLA-B*44 :02),QEGVFHTMW (HLA-B*44 :03) and TASGRVIEEW (HLA-B*58:01), and MHC II epitopes: IIKKFKKDLAAMLRI (HLA-DRB3*02 :02), ENSKMMLELDPPFGD (HLA-DRB3*01:01), HAETWFFDENHPYRT (HLA-DRB3*01:01), TDGVYRVMTRRLLGS (HLA-DRB1*11 :01), and DGCWYGMEIRPRKEP (HLA-DRB5*01:01). Conclusion : This study provides novel potential B cell and T cell epitopes to fight Zika virus infections and may prompt further development of vaccines against ZIKV and other emerging infectious diseases. However, further investigations for protective immune response by in vitro and in vivo studies to ratify the immunogenicity, safety of the predicted structure, and ultimately the vaccine properties to prevent ZIKV infections are warranted.


2021 ◽  
Author(s):  
Daniel S Krauth ◽  
Christina M Jamros ◽  
Shayna C Rivard ◽  
Niels H Olson ◽  
Ryan C Maves

ABSTRACT We describe a patient with subclinical coccidioidomycosis who experienced rapid disease dissemination shortly after SARS-CoV-2 infection, suggesting host immune response dysregulation to coccidioidomycosis by SARS-CoV-2. We hypothesize that disrupted cell-mediated signaling may result after SARS-CoV-2 infection leading to functional exhaustion and CD8+ T-cell senescence with impairment in host cellular response to Coccidioides infection.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ryan D. Pardy ◽  
Stefanie F. Valbon ◽  
Brendan Cordeiro ◽  
Connie M. Krawczyk ◽  
Martin J. Richer

AbstractZika virus (ZIKV) has emerged as an important global health threat, with the recently acquired capacity to cause severe neurological symptoms and to persist within host tissues. We previously demonstrated that an early Asian lineage ZIKV isolate induces a highly activated CD8 T cell response specific for an immunodominant epitope in the ZIKV envelope protein in wild-type mice. Here we show that a contemporary ZIKV isolate from the Brazilian outbreak severely limits CD8 T cell immunity in mice and blocks generation of the immunodominant CD8 T cell response. This is associated with a more sustained infection that is cleared between 7- and 14-days post-infection. Mechanistically, we demonstrate that infection with the Brazilian ZIKV isolate reduces the cross-presentation capacity of dendritic cells and fails to fully activate the immunoproteasome. Thus, our study provides an isolate-specific mechanism of host immune evasion by one Brazilian ZIKV isolate, which differs from the early Asian lineage isolate and provides potential insight into viral persistence associated with recent ZIKV outbreaks.


Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 606
Author(s):  
Giuseppe Cappellano ◽  
Hugo Abreu ◽  
Chiara Casale ◽  
Umberto Dianzani ◽  
Annalisa Chiocchetti

The first vaccines ever made were based on live-attenuated or inactivated pathogens, either whole cells or fragments. Although these vaccines required the co-administration of antigens with adjuvants to induce a strong humoral response, they could only elicit a poor CD8+ T-cell response. In contrast, next-generation nano/microparticle-based vaccines offer several advantages over traditional ones because they can induce a more potent CD8+ T-cell response and, at the same time, are ideal carriers for proteins, adjuvants, and nucleic acids. The fact that these nanocarriers can be loaded with molecules able to modulate the immune response by inducing different effector functions and regulatory activities makes them ideal tools for inverse vaccination, whose goal is to shut down the immune response in autoimmune diseases. Poly (lactic-co-glycolic acid) (PLGA) and liposomes are biocompatible materials approved by the Food and Drug Administration (FDA) for clinical use and are, therefore, suitable for nanoparticle-based vaccines. Recently, another candidate platform for innovative vaccines based on extracellular vesicles (EVs) has been shown to efficiently co-deliver antigens and adjuvants. This review will discuss the potential use of PLGA-NPs, liposomes, and EVs as carriers of peptides, adjuvants, mRNA, and DNA for the development of next-generation vaccines against endemic and emerging viruses in light of the recent COVID-19 pandemic.


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