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

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

Clinical and Developmental Immunology ◽

10.1155/2013/475960 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 13

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.

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Landscape and selection of vaccine epitopes in SARS-CoV-2

Genome Medicine ◽

10.1186/s13073-021-00910-1 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Christof C. Smith ◽

Kelly S. Olsen ◽

Kaylee M. Gentry ◽

Maria Sambade ◽

Wolfgang Beck ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Cell Epitope ◽

T Cell Responses ◽

Sequence Conservation ◽

Conformational Space ◽

T Cell Epitope ◽

T Cell Epitopes ◽

Cell Responses ◽

B Cell Epitope

Abstract Background Early in the pandemic, we designed a SARS-CoV-2 peptide vaccine containing epitope regions optimized for concurrent B cell, CD4+ T cell, and CD8+ T cell stimulation. The rationale for this design was to drive both humoral and cellular immunity with high specificity while avoiding undesired effects such as antibody-dependent enhancement (ADE). Methods We explored the set of computationally predicted SARS-CoV-2 HLA-I and HLA-II ligands, examining protein source, concurrent human/murine coverage, and population coverage. Beyond MHC affinity, T cell vaccine candidates were further refined by predicted immunogenicity, sequence conservation, source protein abundance, and coverage of high frequency HLA alleles. B cell epitope regions were chosen from linear epitope mapping studies of convalescent patient serum, followed by filtering for surface accessibility, sequence conservation, spatial localization near functional domains of the spike glycoprotein, and avoidance of glycosylation sites. Results From 58 initial candidates, three B cell epitope regions were identified. From 3730 (MHC-I) and 5045 (MHC-II) candidate ligands, 292 CD8+ and 284 CD4+ T cell epitopes were identified. By combining these B cell and T cell analyses, as well as a manufacturability heuristic, we proposed a set of 22 SARS-CoV-2 vaccine peptides for use in subsequent murine studies. We curated a dataset of ~ 1000 observed T cell epitopes from convalescent COVID-19 patients across eight studies, showing 8/15 recurrent epitope regions to overlap with at least one of our candidate peptides. Of the 22 candidate vaccine peptides, 16 (n = 10 T cell epitope optimized; n = 6 B cell epitope optimized) were manually selected to decrease their degree of sequence overlap and then synthesized. The immunogenicity of the synthesized vaccine peptides was validated using ELISpot and ELISA following murine vaccination. Strong T cell responses were observed in 7/10 T cell epitope optimized peptides following vaccination. Humoral responses were deficient, likely due to the unrestricted conformational space inhabited by linear vaccine peptides. Conclusions Overall, we find our selection process and vaccine formulation to be appropriate for identifying T cell epitopes and eliciting T cell responses against those epitopes. Further studies are needed to optimize prediction and induction of B cell responses, as well as study the protective capacity of predicted T and B cell epitopes.

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Swine T-Cells and Specific Antibodies Evoked by Peptide Dendrimers Displaying Different FMDV T-Cell Epitopes

Frontiers in Immunology ◽

10.3389/fimmu.2020.621537 ◽

2021 ◽

Vol 11 ◽

Author(s):

Patricia de León ◽

Rodrigo Cañas-Arranz ◽

Sira Defaus ◽

Elisa Torres ◽

Mar Forner ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cell ◽

Cell Epitope ◽

T Cell Epitope ◽

T Cell Epitopes ◽

B Cell Epitope ◽

Mouth Disease Virus ◽

Ifn Γ

Dendrimeric peptide constructs based on a lysine core that comprises both B- and T-cell epitopes of foot-and-mouth disease virus (FMDV) have proven a successful strategy for the development of FMD vaccines. Specifically, B2T dendrimers displaying two copies of the major type O FMDV antigenic B-cell epitope located on the virus capsid [VP1 (140–158)], covalently linked to a heterotypic T-cell epitope from either non-structural protein 3A [3A (21–35)] or 3D [3D (56–70)], named B2T-3A and B2T-3D, respectively, elicit high levels of neutralizing antibodies (nAbs) and IFN-γ-producing cells in pigs. To assess whether the inclusion and orientation of T-3A and T-3D T-cell epitopes in a single molecule could modulate immunogenicity, dendrimers with T epitopes juxtaposed in both possible orientations, i.e., constructs B2TT-3A3D and B2TT-3D3A, were made and tested in pigs. Both dendrimers elicited high nAbs titers that broadly neutralized type O FMDVs, although B2TT-3D3A did not respond to boosting, and induced lower IgGs titers, in particular IgG2, than B2TT-3A3D. Pigs immunized with B2, a control dendrimer displaying two B-cell epitope copies and no T-cell epitope, gave no nABs, confirming T-3A and T-3D as T helper epitopes. The T-3D peptide was found to be an immunodominant, as it produced more IFN-γ expressing cells than T-3A in the in vitro recall assay. Besides, in pigs immunized with the different dendrimeric peptides, CD4+ T-cells were the major subset contributing to IFN-γ expression upon in vitro recall, and depletion of CD4+ cells from PBMCs abolished the production of this cytokine. Most CD4+IFN-γ+ cells showed a memory (CD4+2E3−) and a multifunctional phenotype, as they expressed both IFN-γ and TNF-α, suggesting that the peptides induced a potent Th1 pro-inflammatory response. Furthermore, not only the presence, but also the orientation of T-cell epitopes influenced the T-cell response, as B2TT-3D3A and B2 groups had fewer cells expressing both cytokines. These results help understand how B2T-type dendrimers triggers T-cell populations, highlighting their potential as next-generation FMD vaccines.

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In silico T-cell and B-cell Epitope Based Vaccine Design Against Alphavirus Strain of Chikungunya

Infectious Disorders - Drug Targets ◽

10.2174/1871526519666190521100521 ◽

2020 ◽

Vol 20 (4) ◽

pp. 523-530 ◽

Cited By ~ 1

Author(s):

Maharij Haroon Jadoon ◽

Zainab Rehman ◽

Areeba Khan ◽

Muhammad Rizwan ◽

Sajid Khan ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Cell Epitope ◽

Febrile Illness ◽

Final Analysis ◽

Strong Interactions ◽

T Cell Epitopes ◽

B Cell Epitopes ◽

Hla Alleles ◽

B Cell Epitope

Background: Chikungunya an arbovirus, is transmitted to humans by the bite of Aedes mosquito. The virus occurrences have been reported in Southeast Asian countries including Pakistan. Its symptoms include typical febrile illness and arthralgic syndrome. The virus has not decisively proved to be life-threatening. Methods: The attempt was to design T-cell and B-cell epitope-based vaccine for Chikungunya. The proteome of chikungunya was retrieved, antigenic proteins were identified and T-cell epitopes and B-cell epitopes were predicted. Interacting HLA alleles were also identified. The final analysis was done to confirm that predicted T-cell epitopes and B-cell epitopes can be used as a vaccine. Results: About 32 T-cell epitopes and a 10mer B-cell epitope were identified. Both T-cell and Bcell epitopes demonstrated strong interactions with HLA alleles. The predicted T-cell and B-cell epitopes were docked with respective HLA alleles. The docking analysis showed that the predicted respective epitopes best fit into the binding pockets of the alleles. Conclusion: On the basis of this computational analysis, it is suggested that these predicted epitopes can be used as a remedy against Alphavirus strain of chikungunya. Further laboratory experiments can be conducted to determine the efficacy and stability of this work.

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

Infection and Immunity ◽

10.1128/iai.70.7.3479-3492.2002 ◽

2002 ◽

Vol 70 (7) ◽

pp. 3479-3492 ◽

Cited By ~ 28

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.

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

Frontiers in Oncology ◽

10.3389/fonc.2018.00481 ◽

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

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

Viruses ◽

10.3390/v11050432 ◽

2019 ◽

Vol 11 (5) ◽

pp. 432 ◽

Cited By ~ 6

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.

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

Journal of Immunology Research ◽

10.1155/2017/9363750 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 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.

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

Journal of Dental Research ◽

10.1177/154405910408301209 ◽

2004 ◽

Vol 83 (12) ◽

pp. 936-940 ◽

Cited By ~ 39

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.

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