scholarly journals Immunoinformatic Approach for the identification of T Cell and B Cell Epitopes in the Surface Glycoprotein and Designing a Potent Multiepitope Vaccine Construct Against SARS-CoV-2 including the new UK variant

2021 ◽  
Author(s):  
Kaveri Krishnasamy ◽  
Gracy Fathima Selvaraj ◽  
Kiruba Ramesh ◽  
Padmaoriya Padmanabhan ◽  
Vidya Gopalan ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
T Lymphocyte ◽  
Vaccine Candidate ◽  
Surface Glycoprotein ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
New Variant

The emergence of a novel coronavirus in China in late 2019 has turned into a SARS-CoV-2 pandemic affecting several millions of people worldwide in a short span of time with high fatality. The crisis is further aggravated by the emergence and evolution of new variant SARS-CoV-2 strains in UK during December, 2020 followed by their transmission to other countries. A major concern is that prophylaxis and therapeutics are not available yet to control and prevent the virus which is spreading at an alarming rate, though several vaccine trials are in the final stage. As vaccines are developed through various strategies, their immunogenic potential may drastically vary and thus pose several challenges in offering both arms of immunity such as humoral and cell-mediated immune responses against the virus. In this study, we adopted an immunoinformatics-aided identification of B cell and T cell epitopes in the Spike protein, which is a surface glycoprotein of SARS-CoV-2, for developing a new Multiepitope vaccine construct (MEVC). MEVC has 575 amino acids and comprises adjuvants and various cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes that possess the highest affinity for the respective HLA alleles, assembled and joined by linkers. The computational data suggest that the MEVC is non-toxic, non-allergenic and thermostable with the capability to elicit both humoral and cell-mediated immune responses. The population coverage of various countries affected by COVID-19 with respect to the selected B and T cell epitopes in MEVC was also investigated. Subsequently, the biological activity of MEVC was assessed by bioinformatic tools using the interaction between the vaccine candidate and the innate immune system receptors TLR3 and TLR4. The epitopes of the construct were analyzed with that of the strains belonging to various clades including the new variant UK strain having multiple unique mutations in S protein. Due to the advantageous features, the MEVC can be tested in vitro for more practical validation and the study offers immense scope for developing a potential vaccine candidate against SARS-CoV-2 in view of the public health emergency associated with COVID-19 disease caused by SARS-CoV-2.

scholarly journals Computational Approach for Predicting Common Epitopes in the VP1 Structural Protein of Enterovirus Serotypes EV-D68, EV-D70, and EV-A71

2021 ◽  
Author(s):  
Rihabe Boussettine ◽  
Yassine Kasmi ◽  
Najwa Hassou ◽  
Hlima Bessi ◽  
Moulay Mustapha Ennaji
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Epitope ◽  
Human Enterovirus ◽  
T Cell Epitopes ◽  
Structural Protein ◽  
B Cell Epitopes ◽  
Study Results ◽  
Enterovirus Serotypes

The three human Enterovirus serotypes D-68, D-70, and A-71, are common pathogens that are transmitted by fecal-oral and aerosol routes. These positive RNA viruses were known to exhibit high levels of genetic diversity and variability. Currently, no vaccines are available to protect humans from these three serotypes. Therefore, efforts are needed for the development of a vaccine directed against heterologous viruses. In our study, an immunoinformatics approach is used to identify T- and B-cell epitopes that may help for the generation of a universal vaccine against EV-D70, EV-A71, and EV-D68. B and T cell epitopes were selected based on their length. As a result, 5 B cell epitopes and 18 T cell epitopes were predicted. Our B cell epitope prediction results showed that there are a number of linear regions. Position 150-170 was found to be the most immunogenic for the different strains. Regarding the epitopes of the T lymphocytes, the result of the interactions shows that 95% of the predicted epitopes are common between the 3 sequences and the 5 methods used. These results demonstrate the great immunogenic potential of these sequences and their capacities to trigger immune reactions in people with different HLA alleles. The “VFYDGFAGF” epitope is the most important and most immunogenic for triggering an immune response. Our study results allowed us to identify epitopes to be used in the development of cross-protection vaccines against the three Enterovirus serotypes. However, in vivo and in vitro studies are needed to assess the potential of the epitopes predicted by our study.

scholarly journals Plasmodium vivax Pv12 B-cell epitopes and HLA-DRβ1*-dependent T-cell epitopes in vitro antigenicity

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0203715
Author(s):  
Yoelis Yepes-Pérez ◽  
Carolina López ◽  
Carlos Fernando Suárez ◽  
Manuel Alfonso Patarroyo
Keyword(s):  
T Cell ◽  
B Cell ◽  
Plasmodium Vivax ◽  
T Cell Epitopes ◽  
B Cell Epitopes

scholarly journals Design of a Novel Multi-Epitope Vaccine Against Echinococcus granulosus in Immunoinformatics

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingkai Yu ◽  
Yuejie Zhu ◽  
Yujiao Li ◽  
Zhiqiang Chen ◽  
Tong Sha ◽  
...  
Keyword(s):  
Molecular Docking ◽  
T Cell ◽  
B Cell ◽  
Echinococcus Granulosus ◽  
The Body ◽  
T Cell Epitopes ◽  
Epitope Vaccine ◽  
B Cell Epitopes

All the time, echinococcosis is a global zoonotic disease which seriously endangers public health all over the world. In order to speed up the development process of anti-Echinococcus granulosus vaccine, at the same time, it can also save economic cost. In this study, immunoinformatics tools and molecular docking methods were used to predict and screen the antigen epitopes of Echinococcus granulosus, to design a multi-epitope vaccine containing B- and T-cell epitopes. The multi-epitope vaccine could activate B lymphocytes to produce specific antibodies theoretically, which could protect the human body against Echinococcus granulosus infection. It also could activate T lymphocytes and clear the infected parasites in the body. In this study, four CD8+ T-cell epitopes, three CD4+ T-cell epitopes and four B-cell epitopes of Protein EgTeg were identified by immunoinformatics methods. Meanwhile, three CD8+ T-cell epitopes, two CD4+ T-cell epitopes and four B-cell epitopes of Protein EgFABP1 were identified. We constructed the multi-epitope vaccine using linker proteins. The study based on the traditional methods of antigen epitope prediction, further optimized the prediction results combined with molecular docking technology and improved the precision and accuracy of the results. Finally, in vivo and in vitro experiments had verified that the vaccine designed in this study had good antigenicity and immunogenicity.

scholarly journals Plasmodium vivax Promiscuous T-Helper Epitopes Defined and Evaluated as Linear Peptide Chimera Immunogens

2002 ◽  
Vol 70 (7) ◽  
pp. 3479-3492 ◽  
Author(s):  
Ivette Caro-Aguilar ◽  
Alexandra Rodríguez ◽  
J. Mauricio Calvo-Calle ◽  
Fanny Guzmán ◽  
Patricia De la Vega ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Plasmodium Vivax ◽  
Functional Characterization ◽  
Cell Epitope ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
Linear Peptide ◽  
B Cell Epitope

ABSTRACT Clinical trials of malaria vaccines have confirmed that parasite-derived T-cell epitopes are required to elicit consistent and long-lasting immune responses. We report here the identification and functional characterization of six T-cell epitopes that are present in the merozoite surface protein-1 of Plasmodium vivax (PvMSP-1) and bind promiscuously to four different HLA-DRB1∗ alleles. Each of these peptides induced lymphoproliferative responses in cells from individuals with previous P. vivax infections. Furthermore, linear-peptide chimeras containing the promiscuous PvMSP-1 T-cell epitopes, synthesized in tandem with the Plasmodium falciparum immunodominant circumsporozoite protein (CSP) B-cell epitope, induced high specific antibody titers, cytokine production, long-lasting immune responses, and immunoglobulin G isotype class switching in BALB/c mice. A linear-peptide chimera containing an allele-restricted P. falciparum T-cell epitope with the CSP B-cell epitope was not effective. Two out of the six promiscuous T-cell epitopes exhibiting the highest anti-peptide response also contain B-cell epitopes. Antisera generated against these B-cell epitopes recognize P. vivax merozoites in immunofluorescence assays. Importantly, the anti-peptide antibodies generated to the CSP B-cell epitope inhibited the invasion of P. falciparum sporozoites into human hepatocytes. These data and the simplicity of design of the chimeric constructs highlight the potential of multimeric, multistage, and multispecies linear-peptide chimeras containing parasite promiscuous T-cell epitopes for malaria vaccine development.

scholarly journals Anaplasma marginale Major Surface Protein 2 CD4+-T-Cell Epitopes Are Evenly Distributed in Conserved and Hypervariable Regions (HVR), Whereas Linear B-Cell Epitopes Are Predominantly Located in the HVR

2004 ◽  
Vol 72 (12) ◽  
pp. 7360-7366 ◽  
Author(s):  
Jeffrey R. Abbott ◽  
Guy H. Palmer ◽  
Chris J. Howard ◽  
Jayne C. Hope ◽  
Wendy C. Brown
Keyword(s):  
T Cell ◽  
B Cell ◽  
Surface Protein ◽  
Anaplasma Marginale ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
Major Surface Protein ◽  
Hypervariable Regions ◽  
Major Surface ◽  
Linear B

ABSTRACT Organisms in the genus Anaplasma express an immunodominant major surface protein 2 (MSP2), composed of a central hypervariable region (HVR) flanked by highly conserved regions. Throughout Anaplasma marginale infection, recombination results in the sequential appearance of novel MSP2 variants and subsequent control of rickettsemia by the immune response, leading to persistent infection. To determine whether immune evasion and selection for variant organisms is associated with a predominant response against HVR epitopes, T-cell and linear B-cell epitopes were localized by measuring peripheral blood gamma interferon-secreting cells, proliferation, and antibody binding to 27 overlapping peptides spanning MSP2 in 16 cattle. Similar numbers of MSP2-specific CD4+ T-cell epitopes eliciting responses of similar magnitude were found in conserved and hypervariable regions. T-cell epitope clusters recognized by the majority of animals were identified in the HVR (amino acids [aa] 171 to 229) and conserved regions (aa 101 to 170 and 272 to 361). In contrast, linear B-cell epitopes were concentrated in the HVR, residing within hydrophilic sequences. The pattern of recognition of epitope clusters by T cells and of HVR epitopes by B cells is consistent with the influence of protein structure on epitope recognition.

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.

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