In Silico Vaccine Designing Targeting the Virulence Factors of mce Operons of Mycobacterium avium subsp. Paratuberculosis

2020 ◽  
Vol 17 ◽  
Author(s):  
Taruna Mohinani ◽  
Aditya Saxena ◽  
Shoor Vir Singh
Keyword(s):  
T Cell ◽  
B Cell ◽  
Mycobacterium Avium ◽  
Cellular Localization ◽  
Cell Epitope ◽  
Economic Losses ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
Domestic Livestock ◽  
Mce Operons

Background: Mycobacterium avium sp. paratuberculosis (MAP) causes Paratuberculosis (pTB) in domestic livestock and has also been associated with auto-immune disorders in humans. Infection leads to huge economic losses to the farmers associated with livestock production system worldwide. Currently, search to find proteins with potential to develop as vaccine candidates against MAP are underway. Objective: In this study, we aimed to explore the immunogenicity of the proteins of mammalian cell entry (mce) operons of MAP using computational tools. Method: Genes of mce operons of MAP strain K10 were selected and their orthologs identification was done using VFanalyzer tool. Mce proteins encoded by these operons were analyzed for their antigenicity and sub-cellular localization. Three dimensional structures for Mce proteins were predicted using Phyre2. B cell and T cell epitope analysis was done using methods available at Immune Epitope Database and Analysis Resource. Selection analysis of mce genes was also done. Results: Eight Mce proteins were predicted with B cell and T cell epitopes. Some of them were reported with overlapping B cell and T cell epitopes. We found positively selected sites within some predicted epitopes that indicated some kind of selection pressure by immune system on these protein regions. Some predicted epitopes also had similarity with experimentally identified epitopes of Mce proteins of M. tuberculosis which further strengthened the immunogenic role of Mce proteins. Conclusion: Our findings may potentially assist in the development of effective vaccine against the incurable infection due to MAP bacilli in the domestic livestock species.

scholarly journals Vaccination With a FAT1-Derived B Cell Epitope Combined With Tumor-Specific B and T Cell Epitopes Elicits Additive Protection in Cancer Mouse Models

2018 ◽  
Vol 8 ◽  
Author(s):  
Alberto Grandi ◽  
Laura Fantappiè ◽  
Carmela Irene ◽  
Silvia Valensin ◽  
Michele Tomasi ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Mouse Models ◽  
Cell Epitope ◽  
T Cell Epitopes ◽  
B Cell Epitope

scholarly journals The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 432 ◽  
Author(s):  
Jessica M. van Loben Sels ◽  
Kim Y. Green
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Epitope ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
P Domain ◽  
Capsid Protein Vp1 ◽  
Murine Noroviruses ◽  
Acute Nonbacterial Gastroenteritis ◽  
Insight Into

Human norovirus (HuNoV) is the leading cause of acute nonbacterial gastroenteritis. Vaccine design has been confounded by the antigenic diversity of these viruses and a limited understanding of protective immunity. We reviewed 77 articles published since 1988 describing the isolation, function, and mapping of 307 unique monoclonal antibodies directed against B cell epitopes of human and murine noroviruses representing diverse Genogroups (G). Of these antibodies, 91, 153, 21, and 42 were reported as GI-specific, GII-specific, MNV GV-specific, and G cross-reactive, respectively. Our goal was to reconstruct the antigenic topology of noroviruses in relationship to mapped epitopes with potential for therapeutic use or inclusion in universal vaccines. Furthermore, we reviewed seven published studies of norovirus T cell epitopes that identified 18 unique peptide sequences with CD4- or CD8-stimulating activity. Both the protruding (P) and shell (S) domains of the major capsid protein VP1 contained B and T cell epitopes, with the majority of neutralizing and HBGA-blocking B cell epitopes mapping in or proximal to the surface-exposed P2 region of the P domain. The majority of broadly reactive B and T cell epitopes mapped to the S and P1 arm of the P domain. Taken together, this atlas of mapped B and T cell epitopes offers insight into the promises and challenges of designing universal vaccines and immunotherapy for the noroviruses.

scholarly journals Computer-Aided Design of an Epitope-Based Vaccine against Epstein-Barr Virus

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Julio Alonso-Padilla ◽  
Esther M. Lafuente ◽  
Pedro A. Reche
Keyword(s):  
T Cell ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Epitope ◽  
T Cell Epitopes ◽  
Cell Component ◽  
B Cell Epitopes ◽  
Barr Virus ◽  
Epstein Barr ◽  
Epitope Selection

Epstein-Barr virus is a very common human virus that infects 90% of human adults. EBV replicates in epithelial and B cells and causes infectious mononucleosis. EBV infection is also linked to various cancers, including Burkitt’s lymphoma and nasopharyngeal carcinomas, and autoimmune diseases such as multiple sclerosis. Currently, there are no effective drugs or vaccines to treat or prevent EBV infection. Herein, we applied a computer-aided strategy to design a prophylactic epitope vaccine ensemble from experimentally defined T and B cell epitopes. Such strategy relies on identifying conserved epitopes in conjunction with predictions of HLA presentation for T cell epitope selection and calculations of accessibility and flexibility for B cell epitope selection. The T cell component includes 14 CD8 T cell epitopes from early antigens and 4 CD4 T cell epitopes, targeted during the course of a natural infection and providing a population protection coverage of over 95% and 81.8%, respectively. The B cell component consists of 3 experimentally defined B cell epitopes from gp350 plus 4 predicted B cell epitopes from other EBV envelope glycoproteins, all mapping in flexible and solvent accessible regions. We discuss the rationale for the formulation and possible deployment of this epitope vaccine ensemble.

scholarly journals In Silico Identification and in Vitro Analysis of B and T-Cell Epitopes of the Black Turtle Bean (Phaseolus Vulgaris L.) Lectin

2018 ◽  
Vol 49 (4) ◽  
pp. 1600-1614 ◽  
Author(s):  
Shudong He ◽  
Jinlong Zhao ◽  
Walid Elfalleh ◽  
Mohamed Jemaà ◽  
Hanju  Sun ◽  
...  
Keyword(s):  
Amino Acids ◽  
T Cell ◽  
Phaseolus Vulgaris ◽  
B Cell ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Phaseolus Vulgaris L ◽  
B Cell Epitopes ◽  
B Cell Epitope

Background/Aims: The incidence of lectin allergic disease is increasing in recent decades, and definitive treatment is still lacking. Identification of B and T-cell epitopes of allergen will be useful in understanding the allergen antibody responses as well as aiding in the development of new diagnostics and therapy regimens for lectin poisoning. In the current study, we mainly addressed these questions. Methods: Three-dimensional structure of the lectin from black turtle bean (Phaseolus vulgaris L.) was modeled using the structural template of Phytohemagglutinin from P. vulgaris (PHA-E, PDB ID: 3wcs.1.A) with high identity. The B and T-cell epitopes were screened and identified by immunoinformatics and subsequently validated by ELISA, lymphocyte proliferation and cytokine profile analyses. Results: Seven potential B-cell epitopes (B1 to B7) were identified by sequence and structure based methods, while three T-cell epitopes (T1 to T3) were identified by the predictions of binding score and inhibitory concentration. The epitope peptides were synthesized. Significant IgE binding capability was found in B-cell epitopes (B2, B5, B6 and B7) and T2 (a cryptic B-cell epitope). T1 and T2 induced significant lymphoproliferation, and the release of IL-4 and IL-5 cytokine confirmed the validity of T-cell epitope prediction. Abundant hydrophobic amino acids were found in B-cell epitope and T-cell epitope regions by amino acid analysis. Positively charged amino acids, such as His residue, might be more favored for B-cell epitope. Conclusion: The present approach can be applied for the identification of epitopes in novel allergen proteins and thus for designing diagnostics and therapies in lectin allergy.

Epitope Mapping of Porphyromonas gingivalis Heat-shock Protein and Human Heat-shock Protein in Human Atherosclerosis

2004 ◽  
Vol 83 (12) ◽  
pp. 936-940 ◽  
Author(s):  
J.-I. Choi ◽  
S.-W. Chung ◽  
H.-S. Kang ◽  
B.Y. Rhim ◽  
Y.-M. Park ◽  
...  
Keyword(s):  
T Cell ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
B Cell ◽  
Cell Epitope ◽  
T Cell Epitopes ◽  
Igg Antibody ◽  
B Cell Epitopes ◽  
Human Heat Shock Protein ◽  
Human Hsp60

To identify T- and/or cross-reactive B-cell epitopes of P. gingivalis and human heat-shock protein (HSP)60 in atherosclerosis patients, we synthesized 104 overlapping synthetic peptides spanning whole molecules of P. gingivalis HSP60 and human HSP60, respectively. T-cell epitopes of P. gingivalis HSP were identified with the use of previously established P. gingivalis HSP-reactive T-cell lines. B-cell epitopes of P. gingivalis HSP60 and human HSP60 were identified by the use of patients’ sera. Anti- P. gingivalis, anti- P. gingivalis HSP60, or anti-human HSP60 IgG antibody titers were higher in the atherosclerosis patients compared with the healthy subjects. Five immunodominant peptides of P. gingivalis HSP60, identified as T-cell epitopes, were also found to be B-cell epitopes. Moreover, 6 cross-reactive B-cell epitopes of human HSP60 were identified. It was concluded that P. gingivalis HSP60 might be involved in the immunoregulatory process of atherosclerosis, with common T- and/or B-cell epitope specificities and with cross-reactivity with human HSP60.

scholarly journals B Epitope Multiplicity and B/T Epitope Orientation Influence Immunogenicity of Foot-and-Mouth Disease Peptide Vaccines

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Esther Blanco ◽  
Carolina Cubillos ◽  
Noelia Moreno ◽  
Juan Bárcena ◽  
Beatriz G. de la Torre ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Cell Epitope ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
B Cell Epitope ◽  
Foot And Mouth

Synthetic peptides incorporating protective B- and T-cell epitopes are candidates for new safer foot-and-mouth disease (FMD) vaccines. We have reported that dendrimeric peptides including four copies of a B-cell epitope (VP1 136 to 154) linked to a T-cell epitope (3A 21 to 35) of FMD virus (FMDV) elicit potent B- and T-cell specific responses and confer protection to viral challenge, while juxtaposition of these epitopes in a linear peptide induces less efficient responses. To assess the relevance of B-cell epitope multivalency, dendrimers bearing two (B2T) or four (B4T) copies of the B-cell epitope from type O FMDV (a widespread circulating serotype) were tested in CD1 mice and showed that multivalency is advantageous over simple B-T-epitope juxtaposition, resulting in efficient induction of neutralizing antibodies and optimal release of IFNγ. Interestingly, the bivalent B2T construction elicited similar or even better B- and T-cell specific responses than tetravalent B4T. In addition, the presence of the T-cell epitope and its orientation were shown to be critical for the immunogenicity of the linear juxtaposed monovalent peptides analyzed in parallel. Taken together, our results provide useful insights for a more accurate design of FMD subunit vaccines.

scholarly journals Immunoinformatics Approach Identified Two Highly Conserved B and T Cell Epitopes, LEASKRWAF and DSPLEASKRWAFRTG, for Effective Vaccine Design against Ebola and Marburg Viruses

2019 ◽  
pp. 1-16
Author(s):  
Md. Shahadat Hossain ◽  
Hasan Al. Reza ◽  
Mohammad Shahnoor Hossain
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Simulation Analysis ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Docking Simulation ◽  
Hemorrhagic Fever ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
Mhc Molecules

Aims: Ebola and Marburg viruses cause fatal hemorrhagic fever in both human and non-human primates. Absence of any licensed vaccine has further deteriorated the problem. In the present study, we aimed to design potential epitope based vaccines against these viruses using computational approaches. Methodology: By using various bioinformatics tools and databases, we analyzed the conserved glycoprotein sequences of Ebola and Marburg viruses and predicted two potential epitopes which may be used as peptide vaccines. Results: Using various B-cell and T-cell epitope prediction servers, four highly conserved epitopes were identified. Epitope conservancy analysis showed that  “LEASKRWAF” and “DSPLEASKRWAFRTG” epitopes were 100% and 93.62% conserved and the worldwide population coverage of “LEASKRWAF” interacting with MHC class I molecules and “DSPLEASKRWAFRTG” interacting with MHC class II molecules were 78.74% and 75.75% respectively. Immunoinformatics analysis showed that they are highly immunogenic, flexible and accessible to antibody. Molecular docking simulation analysis demonstrated a very significant interaction between epitopes and MHC molecules with lower binding energy. Cytotoxic analysis and ADMET test also supported their potential as vaccine candidates. Conclusion: In sum, our in silico approach demonstrated that both “LEASKRWAF” and “DSPLEASKRWAFRTG” hold the promise for the development of common vaccine against Ebola and Marburg viruses.

scholarly journals Using Immunoinformatics to Design a mRNA Vaccine against the Spike Glycoprotein of SARS-CoV-2

2021 ◽  
Vol 26 (5) ◽  
pp. 2901-2915
Author(s):  
SHEREEN F. ELKHOLY ◽  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Lymphocyte ◽  
Cell Epitope ◽  
T Cell Epitopes ◽  
Spike Glycoprotein ◽  
Ifn Gamma ◽  
Robust Immune Response ◽  
B Cell Epitope ◽  
Public Health Challenge

The rapid outbreak of the new coronavirus SARS-COV-2 has created a major public health challenge. Immunoinformatics tools had a clear effect in tracking the genetic sequence of the virus and monitoring mutations and design vaccines that are effective enough to produce antibodies. In our study, we resorted to the emerging discipline of immunoinformatics in order to design a multi-epitope mRNA vaccine against the spike glycoprotein of SARS-CoV-2. We screened the B cell and T cell epitopes of the Spike glycoprotein. we used ABC pred server to predict B cell epitope in the spike glycoprotein sequence and we used NetMHC-4.1 server to predict the T-cell epitope. Then we selected the B cell and T cell epitopes that fulfilled the antigenicity, non-toxicity, non-allergenicity, induction of both IL4 and IFN gamma. Finally, we designed multi-epitope mRNA Vaccine construct by linking 6 B lymphocytes epitopes (BL) with 6 cytotoxic T lymphocytes epitopes (CTL) together with helper T lymphocyte (HTL) epitope up-streamed by 5’ cap and down-streamed by poly A tail. The vaccine was found to be antigenic, non-toxic, non-allergenic, capable of generating a robust immune response. Based on these parameters, this design can be considered a promising choice for a vaccine against SARS-CoV-2.

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

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.

scholarly journals SARS-CoV-2 Spike Protein Evolution may Cause Difficulties for Vaccine

2020 ◽  
Author(s):  
Jian Zhou ◽  
Sun Jingjing ◽  
Gang Lu ◽  
Wanchun Wang ◽  
Lin Wang
Keyword(s):  
T Cell ◽  
B Cell ◽  
3D Model ◽  
Bioinformatics Analysis ◽  
Cell Epitope ◽  
Amino Acid Sequences ◽  
T Cell Epitopes ◽  
Sequence Structure ◽  
B Cell Epitopes ◽  
S Protein

Abstract Background: Coronavirus disease 2019 (COVID-19) poses a great threat to human health and life. We performed a bioinformatics analysis to compare the sequence, structure, and epitopes of SARS-CoV-2 spike (S) protein in 10 different countries. Methods: The amino acid sequences of SARS-CoV-2 S protein were obtained from the NCBI database. We used DNASTAR Lasergene software to analyze the protein’s secondary structures. SWISS-MODEL combined with VMD software was used to construct a 3D model of SARS-CoV-2 S protein. DNASTAR Protean and the IEDB database were used to analyze the B cell epitopes and T cell epitopes, respectively. Results: The results of B cell epitopes analysis indicated that the epitopes of SARS-CoV-2 S protein in Korea and American increased, which suggested that the antigenicity of SARS-CoV-2 in Czech, Korea and American might be enhanced. A small number of B cell epitopes disappeared in the SARS-CoV-2 S protein sequence from Greece, Australia, Sweden and India, which suggested that the antigenicity of SARS-CoV-2 in Greece, Australia, Sweden and India may be weakened. T cell epitope analysis indicated that the antigenicity of SARS-CoV-2 in Czech, Korea and American was enhanced, while antigenicity of SARS-CoV-2 in Greece, Australia, Inida, Sweden and Thailand may be weakened. The sequence of SARS-CoV-2 S protein has changed as the virus has spread, and the structures and epitopes have changed accordingly. Conclusion: The mutation leads to a decrease in the antigenicity of SARS-CoV-2, which may be a mechanism for the virus to evade surveillance by the immune system.

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