scholarly journals Quantifying the Persistence of Vaccine-Related T Cell Epitopes in Circulating Swine Influenza A Strains from 2013–2017

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 468
Author(s):  
Swan Tan ◽  
Andres Hazaet Gutiérrez ◽  
Phillip Charles Gauger ◽  
Tanja Opriessnig ◽  
Justin Bahl ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza A ◽  
Cell Epitope ◽  
Swine Influenza ◽  
Swine Flu ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Swine Leukocyte Antigen ◽  
Leukocyte Antigen ◽  
Epitope Vaccines

When swine flu vaccines and circulating influenza A virus (IAV) strains are poorly matched, vaccine-induced antibodies may not protect from infection. Highly conserved T cell epitopes may, however, have a disease-mitigating effect. The degree of T cell epitope conservation among circulating strains and vaccine strains can vary, which may also explain differences in vaccine efficacy. Here, we evaluate a previously developed conserved T cell epitope-based vaccine and determine the persistence of T cell epitope conservation over time. We used a pair-wise homology score to define the conservation between the vaccine’s swine leukocyte antigen (SLA) class I and II-restricted epitopes and T cell epitopes found in 1272 swine IAV strains sequenced between 2013 and 2017. Twenty-four of the 48 total T cell epitopes included in the epitope-based vaccine were highly conserved and found in >1000 circulating swine IAV strains over the 5-year period. In contrast, commercial swine IAV vaccines developed in 2013 exhibited a declining conservation with the circulating IAV strains over the same 5-year period. Conserved T cell epitope vaccines may be a useful adjunct for commercial swine flu vaccines and to improve protection against influenza when antibodies are not cross-reactive.

scholarly journals Mining the capacity of human-associated microorganisms to trigger rheumatoid arthritis—A systematic immunoinformatics analysis of T cell epitopes

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253918
Author(s):  
Jelena Repac ◽  
Marija Mandić ◽  
Tanja Lunić ◽  
Bojan Božić ◽  
Biljana Božić Nedeljković
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
De Novo ◽  
Molecular Mimicry ◽  
Sequence Similarity ◽  
Cell Epitope ◽  
Homology Search ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Painful Condition

Autoimmune diseases, often triggered by infection, affect ~5% of the worldwide population. Rheumatoid Arthritis (RA)–a painful condition characterized by the chronic inflammation of joints—comprises up to 20% of known autoimmune pathologies, with the tendency of increasing prevalence. Molecular mimicry is recognized as the leading mechanism underlying infection-mediated autoimmunity, which assumes sequence similarity between microbial and self-peptides driving the activation of autoreactive lymphocytes. T lymphocytes are leading immune cells in the RA-development. Therefore, deeper understanding of the capacity of microorganisms (both pathogens and commensals) to trigger autoreactive T cells is needed, calling for more systematic approaches. In the present study, we address this problem through a comprehensive immunoinformatics analysis of experimentally determined RA-related T cell epitopes against the proteomes of Bacteria, Fungi, and Viruses, to identify the scope of organisms providing homologous antigenic peptide determinants. By this, initial homology screening was complemented with de novo T cell epitope prediction and another round of homology search, to enable: i) the confirmation of homologous microbial peptides as T cell epitopes based on the predicted binding affinity to RA-related HLA polymorphisms; ii) sequence similarity inference for top de novo T cell epitope predictions to the RA-related autoantigens to reveal the robustness of RA-triggering capacity for identified (micro/myco)organisms. Our study reveals a much larger repertoire of candidate RA-triggering organisms, than previously recognized, providing insights into the underestimated role of Fungi in autoimmunity and the possibility of a more direct involvement of bacterial commensals in RA-pathology. Finally, our study pinpoints Endoplasmic reticulum chaperone BiP as the most potent (most likely mimicked) RA-related autoantigen, opening an avenue for identifying the most potent autoantigens in a variety of different autoimmune pathologies, with possible implications in the design of next-generation therapeutics aiming to induce self-tolerance by affecting highly reactive autoantigens.

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.

scholarly journals HLA-B*35-Restricted CD8+-T-Cell Epitope in Mycobacterium tuberculosis Rv2903c

2002 ◽  
Vol 70 (2) ◽  
pp. 981-984 ◽  
Author(s):  
Michèl R. Klein ◽  
Abdulrahman S. Hammond ◽  
Steve M. Smith ◽  
Assan Jaye ◽  
Pauline T. Lukey ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Mycobacterial Antigens ◽  
Necrosis Factor

ABSTRACT Few human CD8+ T-cell epitopes in mycobacterial antigens have been described to date. Here we have identified a novel HLA-B*35-restricted CD8+ T-cell epitope in Mycobacterium tuberculosis Rv2903c based on a reverse immunogenetics approach. Peptide-specific CD8 T cells were able to kill M. tuberculosis-infected macrophages and produce gamma interferon and tumor necrosis factor alpha.

Definition of a human T cell epitope from influenza A non-structural protein 1 using HLA-A2.1 transgenic mice

1995 ◽  
Vol 7 (4) ◽  
pp. 597-605 ◽  
Author(s):  
Stephen Man ◽  
Michael H. Newberg ◽  
Victoria L. Crotzer ◽  
C. John Luckey ◽  
Noelle S. Williams ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
Influenza A ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
Structural Protein ◽  
Human T Cell ◽  
Definition Of ◽  
Hla A2.1

scholarly journals Conservation and Diversity of Influenza A H1N1 HLA-Restricted T Cell Epitope Candidates for Epitope-Based Vaccines

PLoS ONE ◽  
2010 ◽  
Vol 5 (1) ◽  
pp. e8754 ◽  
Author(s):  
Paul ThiamJoo Tan ◽  
A. T. Heiny ◽  
Olivo Miotto ◽  
Jerome Salmon ◽  
Ernesto T. A. Marques ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza A ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
Influenza A H1n1

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 Screening of HLA-A restricted T cell epitopes of SARS-CoV-2 and induction of CD8+ T cell responses in HLA-A transgenic mice

2021 ◽  
Author(s):  
Xiaoxiao Jin ◽  
Ding Yan ◽  
Sun Shihui ◽  
Xinyi Wang ◽  
Zining Zhou ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
Cell Epitope ◽  
T Cell Responses ◽  
Poly I:C ◽  
T Cell Epitopes ◽  
Cell Responses ◽  
Mhc Class I Molecule ◽  
Healthy Donors ◽  
Epitope Vaccines

AbstractWhile SARS-CoV-2-specific T cells have been characterized to play essential roles in host immune protection in COVID-19 patients, few researches focus on the functional validation of T cell epitopes and development of vaccines inducing specific T cell responses. In this study, 120 CD8+ T cell epitopes from E, M, N, S and RdRp proteins of SARS-CoV-2 were validated by on-silicon prediction, DC-peptide-PBL costimulation with healthy donors’ PBMCs and HLA-A molecule competitive binding experiments. Among them, 110, 15, 6, 14 and 12 epitopes were highly homologous with SARS-CoV, OC43, NL63, HKU1, and 229E, respectively. Thirty-one epitopes restricted by HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C), R848 or polylactic-co-glycolic acid nanoparticles, which elicited robust specific CD8+ T cell responses in wild-type and HLA-A2/DR1 transgenic mice. Seven of the 31 epitopes were found to be cross-presented by HLA-A2 and H-2K/Db molecules. These data have provided a library of SARS-CoV-2 CD8+ T cell epitopes which restricted by a series of high-frequency HLA-A allotypes and covered broad population in Asia, and initially confirmed the feasibility of human MHC class I molecule-restricted SARS-CoV2 epitope peptide cocktail vaccines, thus will facilitate the development of T cell epitope vaccines and specific cellular function detection kits.

scholarly journals Construction and efficacy evaluation of novel swine leukocyte antigen (SLA) class I and class II allele-specific poly-T cell epitope vaccines against porcine reproductive and respiratory syndrome virus

2020 ◽  
Vol 101 (11) ◽  
pp. 1191-1201
Author(s):  
Debin Tian ◽  
Sakthivel Subramaniam ◽  
C. Lynn Heffron ◽  
Hassan M. Mahsoub ◽  
Harini Sooryanarain ◽  
...  
Keyword(s):  
T Cell ◽  
Statistical Significance ◽  
Cell Epitope ◽  
Class Ii ◽  
Class I ◽  
Respiratory Syndrome Virus ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Efficacy Evaluation ◽  
Allele Specific

Porcine reproductive and respiratory syndrome virus (PRRSV) causes an economically important global swine disease. Here we report the development of subunit PRRSV-2 vaccines by expressing swine leucocyte antigen (SLA) class I and class II allele-specific epitope antigens in a robust adenovirus vector. SLA I-specific CD8 and SLA II-specific CD4 T cell epitopes of PRRSV-2 NADC20 were predicted in silico. Stable murine leukaemia cell lines (RMA-S), which are TAP-deficient and lacking endogenous class I epitope loading, were established to express different SLA I alleles. The binding stability of PRRSV T cell epitope peptides with SLA I alleles expressed on RMA-S cells was characterized. Two PRRSV poly-T cell epitope peptides were designed. NADC20-PP1 included 39 class I epitopes, consisting of 8 top-ranked epitopes specific to each of 5 SLA I alleles, and fused to 5 class II epitopes specific to SLA II alleles. NADC20-PP2, a subset of PP1, included two top-ranked class I epitopes specific to each of the five SLA I alleles. Two vaccine candidates, Ad-NADC20-PP1 and Ad-NADC20-PP2, were constructed by expressing the polytope peptides in a replication-incompetent human adenovirus 5 vector. A vaccination and challenge study in 30 piglets showed that animals vaccinated with the vaccines had numerically lower gross and histopathology lung lesions, and numerically lower PRRSV RNA loads in lung and serum after challenge compared to the controls, although there was no statistical significance. The results suggested that the Ad-NADC20-PP1 and Ad-NADC20-PP2 vaccines provided little or no protection, further highlighting the tremendous challenges faced in developing an effective subunit PRRSV-2 vaccine.

scholarly journals T Cell Epitope-Based Vaccine Design for Pandemic Novel Coronavirus 2019-nCoV

2020 ◽  
Author(s):  
Dr. Seema Mishra
Keyword(s):  
T Cell ◽  
Cell Epitope ◽  
Structural Proteins ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Consensus Sequences ◽  
Tight Cluster ◽  
Cell Assays ◽  
Novel Coronavirus

Immunoinformatics approach has been used to identify potential T cell epitopes from structural and non-structural proteins for immunotherapy against novel coronavirus 2019-nCoV across populations Two different prediction algorithms, NetCTLpan and Pickpocket were used to generate consensus epitopes against HLA supertypes. All of the 57 epitopes identified had no similarity/identity with the human proteome thus preventing crossreactivity. Many of these epitopes formed a tight cluster around consensus sequences <p>MGYINVFAFPFTIYSLLLC and KVSIWNLDYIINLI across proteins and alleles. These should be urgently tested in <i>in-vitro</i> MHC binding and T cell assays before being tried as vaccines to further prevent pandemic due to this lethal coronavirus.<br></p>

Sign in / Sign up

Export Citation Format

Share Document