Computational Prediction of Usutu Virus E Protein B Cell and T Cell Epitopes for Potential Vaccine Development

AbstractThe beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the available SARS-CoV-2 sequences (as of 9 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.

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Design of Peptide Vaccine for COVID19: CD8+ and CD4+ T cell epitopes from SARS-CoV-2 open-reading-frame protein variants

10.1101/2021.09.21.461301 ◽

2021 ◽

Author(s):

Simone Parn ◽

Gabriel Jabbour ◽

Vincent Nguyenkhoa ◽

Sivanesan Dakshanamurthy

Keyword(s):

T Cell ◽

Vaccine Development ◽

Human Life ◽

Peptide Vaccine ◽

T Cell Response ◽

Cd4 T Cell ◽

World Population ◽

T Cell Epitopes ◽

The World ◽

Potential Vaccine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has challenged public health at an unprecedented scale which has led to a dramatic loss of human life worldwide. To design a protective vaccine against SARS-CoV-2, it is necessary to understand which SARS-CoV-2 specific epitopes can elicit a T cell response and provide protection across a broad population. In this study, PLpro and RdRp, two immunogenic non-structural proteins from an immunodominant gene region ORF1ab, as well as ORF3a and ORF9b are identified as potential vaccine targets against SARS-CoV-2. To select top epitopes for vaccine design, we used various clinical properties, such as antigenicity, allergenicity, toxicity and IFN-y secretion. The analysis of CD8 and CD4 T cell epitopes revealed multiple potential vaccine constructs that cover a high percentage of the world population. We identified 8 immunogenic, antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD8 proteins for nsp3, 4 for nsp12, 11 for ORF3a and 3 for ORF9b that are common across four lineages of variants of concern: B.1.1.7, P.1, B.1.351 and B.1.617.2, which protect 98.12%, 87.08%, 96.07% and 63.8% of the world population, respectively. We also identified variant specific T cell epitopes that could be useful in targeting each variant strain separately. Including the prediction of mouse MHC affinity towards our top CD8 epitopes, our study revealed a total of 3 immunogenic, antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD8 epitopes overlapping with 6 antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD4 epitopes across all four variants of concern which can effectively be utilized in pre-clinical studies. The landscape of SARS-CoV-2 T cell epitopes that we identified can help lead SARS-CoV-2 vaccine development as well as epitope-based peptide vaccine research in the future.

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Designing multiepitope-based vaccine against Eimeria from immune mapped protein 1 (IMP-1) antigen using immunoinformatic approach

Scientific Reports ◽

10.1038/s41598-021-97880-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Thabile Madlala ◽

Victoria T. Adeleke ◽

Abiodun J. Fatoba ◽

Moses Okpeku ◽

Adebayo A. Adeniyi ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Vaccine Development ◽

Cell Epitope ◽

Docking Simulation ◽

Cost Effective ◽

Economic Loss ◽

T Cell Epitopes ◽

Live Vaccines ◽

Physiochemical Parameters

AbstractDrug resistance against coccidiosis has posed a significant threat to chicken welfare and productivity worldwide, putting daunting pressure on the poultry industry to reduce the use of chemoprophylactic drugs and live vaccines in poultry to treat intestinal diseases. Chicken coccidiosis, caused by an apicomplexan parasite of Eimeria spp., is a significant challenge worldwide. Due to the experience of economic loss in production and prevention of the disease, development of cost-effective vaccines or drugs that can stimulate defence against multiple Eimeria species is imperative to control coccidiosis. This study explored Eimeria immune mapped protein-1 (IMP-1) to develop a multiepitope-based vaccine against coccidiosis by identifying antigenic T-cell and B-cell epitope candidates through immunoinformatic techniques. This resulted in the design of 7 CD8+, 21 CD4+ T-cell epitopes and 6 B-cell epitopes, connected using AAY, GPGPG and KK linkers to form a vaccine construct. A Cholera Toxin B (CTB) adjuvant was attached to the N-terminal of the multiepitope construct to improve the immunogenicity of the vaccine. The designed vaccine was assessed for immunogenicity (8.59968), allergenicity and physiochemical parameters, which revealed the construct molecular weight of 73.25 kDa, theoretical pI of 8.23 and instability index of 33.40. Molecular docking simulation of vaccine with TLR-5 with binding affinity of − 151.893 kcal/mol revealed good structural interaction and stability of protein structure of vaccine construct. The designed vaccine predicts the induction of immunity and boosted host's immune system through production of antibodies and cytokines, vital in hindering surface entry of parasites into host. This is a very important step in vaccine development though further experimental study is still required to validate these results.

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Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome

10.1101/2020.05.14.093757 ◽

2020 ◽

Author(s):

Stephen N. Crooke ◽

Inna G. Ovsyannikova ◽

Richard B. Kennedy ◽

Gregory A. Poland

Keyword(s):

T Cell ◽

B Cell ◽

Selection Criteria ◽

Vaccine Development ◽

Hla Class I ◽

Class Ii ◽

Class I ◽

T Cell Epitopes ◽

B Cell Epitopes ◽

Novel Coronavirus

AbstractA novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across the globe, infecting millions of people and generating societal disruption on a level not seen since the 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth knowledge on betacoronavirus immunology. To that end, we developed a computational workflow using a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. Using increasingly stringent selection criteria to select peptides with significant HLA promiscuity and predicted antigenicity, we identified 41 potential T cell epitopes (5 HLA class I, 36 HLA class II) and 6 potential B cell epitopes, respectively. Docking analysis and binding predictions demonstrated enrichment for peptide binding to HLA-B (class I) and HLA-DRB1 (class II) molecules. Overlays of predicted B cell epitopes with the structure of the viral spike (S) glycoprotein revealed that 4 of 6 epitopes were located in the receptor-binding domain of the S protein. To our knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for vaccine development.Significance StatementThe novel coronavirus SARS-CoV-2 recently emerged from China, rapidly spreading and ushering in a global pandemic. Despite intensive research efforts, our knowledge of SARS-CoV-2 immunology and the proteins targeted by the immune response remains relatively limited, making it difficult to rationally design candidate vaccines. We employed a suite of bioinformatic tools, computational algorithms, and structural modeling to comprehensively analyze the entire SARS-CoV-2 proteome for potential T cell and B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41 T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen.

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Computational perspectives revealed prospective vaccine candidates from five structural proteins of novel SARS corona virus 2019 (SARS-CoV-2)

PeerJ ◽

10.7717/peerj.9855 ◽

2020 ◽

Vol 8 ◽

pp. e9855

Author(s):

Rajesh Anand ◽

Subham Biswal ◽

Renu Bhatt ◽

Bhupendra N. Tiwary

Keyword(s):

T Cell ◽

B Cell ◽

Structural Proteins ◽

T Cell Epitopes ◽

Population Coverage ◽

B Cell Epitopes ◽

Vaccine Candidates ◽

Conformational Epitopes ◽

Potential Vaccine ◽

Linear B

Background The present pandemic COVID-19 is caused by SARS-CoV-2, a single-stranded positive-sense RNA virus from the Coronaviridae family. Due to a lack of antiviral drugs, vaccines against the virus are urgently required. Methods In this study, validated computational approaches were used to identify peptide-based epitopes from six structural proteins having antigenic properties. The Net-CTL 1.2 tool was used for the prediction of CD8+ T-cell epitopes, while the robust tools Bepi-Pred 2 and LBtope was employed for the identification of linear B-cell epitopes. Docking studies of the identified epitopes were performed using HADDOCK 2.4 and the structures were visualized by Discovery Studio and LigPlot+. Antigenicity, immunogenicity, conservancy, population coverage and allergenicity of the predicted epitopes were determined by the bioinformatics tools like VaxiJen v2.0 server, the Immune Epitope Database tools and AllerTOP v.2.0, AllergenFP 1.0 and ElliPro. Results The predicted T cell and linear B-cell epitopes were considered as prime vaccine targets in case they passed the requisite parameters like antigenicity, immunogenicity, conservancy, non-allergenicity and broad range of population coverage. Among the predicted CD8+ T cell epitopes, potential vaccine targets from surface glycoprotein were; YQPYRVVVL, PYRVVVLSF, GVYFASTEK, QLTPTWRVY, and those from ORF3a protein were LKKRWQLAL, HVTFFIYNK. Similarly, RFLYIIKLI, LTWICLLQF from membrane protein and three epitopes viz; SPRWYFYYL, TWLTYTGAI, KTFPPTEPK from nucleocapsid phosphoprotein were the superior vaccine targets observed in our study. The negative values of HADDOCK and Z scores obtained for the best cluster indicated the potential of the epitopes as suitable vaccine candidates. Analysis of the 3D and 2D interaction diagrams of best cluster produced by HADDOCK 2.4 displayed the binding interaction of leading T cell epitopes within the MHC-1 peptide binding clefts. On the other hand, among linear B cell epitopes the majority of potential vaccine targets were from nucleocapsid protein, viz; 59−HGKEDLKFPRGQGVPINTNSSPDDQIGYYRRATRRIRGGDGKMKDLS−105, 227−LNQLE SKMSGKGQQQQGQTVTKKSAAEASKKPRQKRTATK−266, 3−DNGPQNQRNAPRITFGGP−20, 29−GERSGARSKQRRPQGL−45. Two other prime vaccine targets, 370−NSASFSTFKCYGVSPTKLNDLCFTNV−395 and 260−AGAAAYYVGYLQPRT−274 were identified in the spike protein. The potential B-cell conformational epitopes were predicted on the basis of a higher protrusion index indicating greater solvent accessibility. These conformational epitopes were of various lengths and belonged to spike, ORF3a, membrane and nucleocapsid proteins. Conclusions Taken together, eleven T cell epitopes, seven B cell linear epitopes and ten B cell conformational epitopes were identified from five structural proteins of SARS-CoV-2 using advanced computational tools. These potential vaccine candidates may provide important timely directives for an effective vaccine against SARS-CoV-2.

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In silico identification of immunodominant B-cell and T-cell epitopes of non-structural proteins of Usutu Virus

Microbial Pathogenesis ◽

10.1016/j.micpath.2018.09.019 ◽

2018 ◽

Vol 125 ◽

pp. 129-143 ◽

Cited By ~ 5

Author(s):

Rohit Satyam ◽

Essam Mohammed Janahi ◽

Tulika Bhardwaj ◽

Pallavi Somvanshi ◽

Shafiul Haque ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

In Silico ◽

Structural Proteins ◽

T Cell Epitopes ◽

Usutu Virus ◽

In Silico Identification

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Landscape and Selection of Vaccine Epitopes in SARS-CoV-2

10.1101/2020.06.04.135004 ◽

2020 ◽

Cited By ~ 6

Author(s):

Christof C. Smith ◽

Sarah Entwistle ◽

Caryn Willis ◽

Steven Vensko ◽

Wolfgang Beck ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Epitope Mapping ◽

Cell Epitope ◽

Computational Prediction ◽

Sequence Conservation ◽

Cell Vaccine ◽

T Cell Epitopes ◽

Peptide Vaccines ◽

B Cell Epitope

AbstractThere is an urgent need for a vaccine with efficacy against SARS-CoV-2. We hypothesize that peptide vaccines containing epitope regions optimized for concurrent B cell, CD4+ T cell, and CD8+ T cell stimulation would drive both humoral and cellular immunity with high specificity, potentially avoiding undesired effects such as antibody-dependent enhancement (ADE). Additionally, such vaccines can be rapidly manufactured in a distributed manner. In this study, we combine computational prediction of T cell epitopes, recently published B cell epitope mapping studies, and epitope accessibility to select candidate peptide vaccines for SARS-CoV-2. We begin with an exploration of the space of possible T cell epitopes in SARS-CoV-2 with interrogation of predicted HLA-I and HLA-II ligands, overlap between predicted ligands, protein source, as well as concurrent human/murine coverage. Beyond MHC affinity, T cell vaccine candidates were further refined by predicted immunogenicity, viral source protein abundance, sequence conservation, coverage of high frequency HLA alleles and co-localization of CD4+ and CD8+ T cell epitopes. B cell epitope regions were chosen from linear epitope mapping studies of convalescent patient serum, followed by filtering to select regions with surface accessibility, high sequence conservation, spatial localization near functional domains of the spike glycoprotein, and avoidance of glycosylation sites. From 58 initial candidates, three B cell epitope regions were identified. By combining these B cell and T cell analyses, as well as a manufacturability heuristic, we propose a set of SARS-CoV-2 vaccine peptides for use in subsequent murine studies and clinical trials.Abstract Figure

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COVID-19 Vaccine Candidates by Identification of B and T Cell Multi-Epitopes Against SARS-COV-2

10.20944/preprints202008.0092.v1 ◽

2020 ◽

Author(s):

Suresh Kumar ◽

Sarmilah Mathavan ◽

Wee Jia Jin ◽

Nur Azznira Bt Azman ◽

Devindren Subramanaiam ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Vaccine Development ◽

Clinical Symptoms ◽

Early Stage ◽

Consensus Sequence ◽

Cell Epitope ◽

Specific Treatment ◽

T Cell Epitopes ◽

Binding Prediction

Coronavirus disease (COVID-19) is a new discovered strain where WHO officially declares the disease as COVID-19 while the virus responsible for it called Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2. The incubation period of this disease is between 14 days. Ordinary clinical symptoms that reported around the world include fever, cough, fatigue, diarrhoea and vomiting as well as asymptomatic for certain people. Infection is spread mainly through broad droplets. In early March 2020, WHO again has announced that COVID-19 is a pandemic with currently no specific treatment. The potential use of SARS-COV-2 proteome as a vaccine candidate by analysing through B-cell and T-cell antigenicity by using a immunoinformatics approach as a vaccine development early stage. In this study, we used consensus sequence for SARS-COV-2 proteome that was retrieved from NCBI database. VaxiJen 2.0 was mainly used to identify the antigenic property of SARS-COV-2 proteins. IEDB then used to analyse the B-cell epitope, the presence of T cell immunogenic epitope in SARS-COV-2 proteins was obtained by using compromise method of MHC class I and II tools that accessible respectively using ProPred-1 server and MHC II Binding Prediction in IEDB database. The best epitopes of B and T-cell epitopes were predicted with high antigencity and the information is disseminated through web-based database resource (https://covid-19.omicstutorials.com/epitopes/). This study will be useful to find a new epitope-based candidate for SARS-COV-2. However, further study needs to be done for the next stages of vaccine development.

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Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies

Viruses ◽

10.3390/v12030254 ◽

2020 ◽

Vol 12 (3) ◽

pp. 254 ◽

Cited By ~ 367

Author(s):

Syed Faraz Ahmed ◽

Ahmed A. Quadeer ◽

Matthew R. McKay

Keyword(s):

T Cell ◽

B Cell ◽

T Cell Epitopes ◽

Population Coverage ◽

Preliminary Identification ◽

Coverage Analysis ◽

Potential Vaccine ◽

Novel Virus ◽

Novel Coronavirus ◽

Mhc Alleles

The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.

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In silico structural analysis of Hantaan virus glycoprotein G2 and conserved epitope prediction for vaccine development

Journal of Applied Virology ◽

10.21092/jav.v3i3.38 ◽

2014 ◽

Vol 3 (3) ◽

pp. 62 ◽

Cited By ~ 1

Author(s):

Monzilur Rahman ◽

Md. Masud Parvege

Keyword(s):

T Cell ◽

B Cell ◽

Structural Model ◽

Vaccine Development ◽

3D Structure ◽

Hemorrhagic Fever ◽

Hantaan Virus ◽

Sequence Information ◽

T Cell Epitopes ◽

Number Of Patients

<p>Hantaan virus (HNTV) is an etiological agent of potentially fatal hemorrhagic fever with renal syndrome (HFRS). The virus infects a large number of patients annually with a mortality rate more than 10%. However, no treatment option or vaccine is available against the virus. Between two envelope proteins, HNTV glycoprotein G2 has higher antigenicity making it a better target for vaccine development. However, 3-D structure of the protein is not available which is important for identifying epitopes that are essential for vaccine design. Therefore, this study was designed to predict a structural model of glycoprotein G2 and to predict peptide sequences for vaccine development containing conserved epitopes within the structure. Many of the physio-chemical and structural properties including secondary structure and di-sulfide linkage of the protein were predicted using a number of computational tools. <strong></strong>The 3D structure of the protein was modeled using I-TASSER online tool. The quality of the predicted models was evaluated with Ramachandran plot and Z-score. The structural and sequence information was used to predict B-cell and T-cell epitopes on glycoprotein G2. Using various bio-informatics and immuno-informatics tools, a total of 9 continuous B-cell and 22 T-cell epitopes were predicted having significant antigenicity. These antigenic epitopes were further analyzed for conservation and a total of 4 B-cells and 8 T-cell epitopes were found to be highly conserved in sequences from diverse origins. These epitopes revealed by the current study are recognized by immune system to protect host from HNTV infection can be potential targets for vaccine development.</p>

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