474 results on '"T cell epitopes"'
Search Results
2. T Cell Peptide Prediction, Immune Response, and Host–Pathogen Relationship in Vaccinated and Recovered from Mild COVID-19 Subjects.
- Author
-
Macchia, Iole, La Sorsa, Valentina, Ciervo, Alessandra, Ruspantini, Irene, Negri, Donatella, Borghi, Martina, De Angelis, Maria Laura, Luciani, Francesca, Martina, Antonio, Taglieri, Silvia, Durastanti, Valentina, Altavista, Maria Concetta, Urbani, Francesca, and Mancini, Fabiola more...
- Subjects
- *
PEPTIDES , *CELLULAR immunity , *SARS-CoV-2 Omicron variant , *VACCINE development , *ANTIBODY formation , *T cells - Abstract
COVID-19 remains a significant threat, particularly to vulnerable populations. The emergence of new variants necessitates the development of treatments and vaccines that induce both humoral and cellular immunity. This study aimed to identify potentially immunogenic SARS-CoV-2 peptides and to explore the intricate host–pathogen interactions involving peripheral immune responses, memory profiles, and various demographic, clinical, and lifestyle factors. Using in silico and experimental methods, we identified several CD8-restricted SARS-CoV-2 peptides that are either poorly studied or have previously unreported immunogenicity: fifteen from the Spike and three each from non-structural proteins Nsp1-2-3-16. A Spike peptide, LA-9, demonstrated a 57% response rate in ELISpot assays using PBMCs from 14 HLA-A*02:01 positive, vaccinated, and mild-COVID-19 recovered subjects, indicating its potential for diagnostics, research, and multi-epitope vaccine platforms. We also found that younger individuals, with fewer vaccine doses and longer intervals since infection, showed lower anti-Spike (ELISA) and anti-Wuhan neutralizing antibodies (pseudovirus assay), higher naïve T cells, and lower central memory, effector memory, and CD4hiCD8low T cells (flow cytometry) compared to older subjects. In our cohort, a higher prevalence of Vδ2-γδ and DN T cells, and fewer naïve CD8 T cells, seemed to correlate with strong cellular and lower anti-NP antibody responses and to associate with Omicron infection, absence of confusional state, and habitual sporting activity. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
Catalog
3. Preclinical immunogenicity risk assessment of biotherapeutics using CD4 T cell assays.
- Author
-
Walsh, Robin E., Nix, Angela, Ackaert, Chloé, Mazy, Aurélie, Schockaert, Jana, Pattyn, Sofie, and Malherbe, Laurent
- Subjects
T cells ,MONONUCLEAR leukocytes ,IMMUNE response ,CD4 antigen ,RISK assessment - Abstract
T-cell dependent antibody responses to biotherapeutics remain a challenge to the optimal clinical application of biotherapeutics because of their capacity to impair drug efficacy and their potential to cause safety issues. To minimize this clinical immunogenicity risk, preclinical assays measuring the capacity of biotherapeutics to elicit CD4 T cell response in vitro are commonly used. However, there is considerable variability in assay formats and a general poor understanding of their respective predictive value. In this study, we evaluated the performance of three different CD4 T cell proliferation assays in their capacity to predict clinical immunogenicity: a CD8 T cell depleted peripheral blood mononuclear cells (PBMC) assay and two co-culture-based assays between dendritic cells (DCs) and autologous CD4 T cells with or without restimulation with monocytes. A panel of 10 antibodies with a wide range of clinical immunogenicity was selected. The CD8 T cell depleted PBMC assay predicted the clinical immunogenicity in four of the eight highly immunogenic antibodies included in the panel. Similarly, five antibodies with high clinical immunogenicity triggered a response in the DC: CD4 T cell assay but the responses were of lower magnitude than the ones observed in the PBMC assay. Remarkably, three antibodies with high clinical immunogenicity did not trigger any response in either platform. The addition of a monocyte restimulation step to the DC: CD4 T cell assay did not further improve its predictive value. Overall, these results indicate that there are no CD4 T cell assay formats that can predict the clinical immunogenicity of all biotherapeutics and reinforce the need to combine results from various preclinical assays assessing antigen uptake and presentation to fully mitigate the immunogenicity risk of biotherapeutics. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
4. Regional Variation of the CD4 and CD8 T Cell Epitopes Conserved in Circulating Dengue Viruses and Shared with Potential Vaccine Candidates.
- Author
-
Chawla, Yadya M., Bajpai, Prashant, Saini, Keshav, Reddy, Elluri Seetharami, Patel, Ashok Kumar, Murali-Krishna, Kaja, and Chandele, Anmol
- Subjects
- *
DENGUE viruses , *T cells , *EPITOPES , *CD8 antigen , *CD4 antigen , *VACCINE trials , *FENITROTHION - Abstract
As dengue expands globally and many vaccines are under trials, there is a growing recognition of the need for assessing T cell immunity in addition to assessing the functions of neutralizing antibodies during these endeavors. While several dengue-specific experimentally validated T cell epitopes are known, less is understood about which of these epitopes are conserved among circulating dengue viruses and also shared by potential vaccine candidates. As India emerges as the epicenter of the dengue disease burden and vaccine trials commence in this region, we have here aligned known dengue specific T cell epitopes, reported from other parts of the world with published polyprotein sequences of 107 dengue virus isolates available from India. Of the 1305 CD4 and 584 CD8 epitopes, we found that 24% and 41%, respectively, were conserved universally, whereas 27% and 13% were absent in any viral isolates. With these data, we catalogued epitopes conserved in circulating dengue viruses from India and matched them with each of the six vaccine candidates under consideration (TV003, TDEN, DPIV, CYD-TDV, DENVax and TVDV). Similar analyses with viruses from Thailand, Brazil and Mexico revealed regional overlaps and variations in these patterns. Thus, our study provides detailed and nuanced insights into regional variation that should be considered for itemization of T cell responses during dengue natural infection and vaccine design, testing and evaluation. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
5. Cross-Reactivity Assessment of Vaccine-Derived SARS-CoV-2 T Cell Responses against BA.2.86 and JN.1.
- Author
-
Sohail, Muhammad Saqib, Ahmed, Syed Faraz, Quadeer, Ahmed Abdul, and McKay, Matthew R.
- Subjects
- *
T cells , *SARS-CoV-2 , *SARS-CoV-2 Omicron variant , *CELLULAR recognition , *BOOSTER vaccines , *CROSS reactions (Immunology) - Abstract
The SARS-CoV-2 Omicron sub-variants BA.2.86 and JN.1 contain multiple mutations in the spike protein that were not present in previous variants of concern and Omicron sub-variants. Preliminary research suggests that these variants reduce the neutralizing capability of antibodies induced by vaccines, which is particularly significant for JN.1. This raises concern as many widely deployed COVID-19 vaccines are based on the spike protein of the ancestral Wuhan strain of SARS-CoV-2. While T cell responses have been shown to be robust against previous SARS-CoV-2 variants, less is known about the impact of mutations in BA.2.86 and JN.1 on T cell responses. We evaluate the effect of mutations specific to BA.2.86 and JN.1 on experimentally determined T cell epitopes derived from the spike protein of the ancestral Wuhan strain and the spike protein of the XBB.1.5 strain that has been recommended as a booster vaccine. Our data suggest that BA.2.86 and JN.1 affect numerous T cell epitopes in spike compared to previous variants; however, the widespread loss of T cell recognition against these variants is unlikely. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
6. To stay or not to stay intact as an allergen: the endolysosomal degradation assay used as tool to analyze protein immunogenicity and T cell epitopes
- Author
-
Elif Öztemiz Topcu and Gabriele Gadermaier
- Subjects
endolysosomal degradation assay ,antigen processing ,allergens ,T cell epitopes ,mass spectrometry ,immunogenicity ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Antigen uptake and processing of exogenous proteins is critical for adaptive immunity, particularly for T helper cell activation. Proteins undergo distinct proteolytic processing in endolysosomal compartments of antigen-presenting cells. The resulting peptides are presented on MHC class II molecules and specifically recognized by T cells. The in vitro endolysosomal degradation assay mimics antigen processing by incubating a protein of interest with a protease cocktail derived from the endolysosomal compartments of antigen presenting cells. The kinetics of protein degradation is monitored by gel electrophoresis and allows calculation of a protein's half-life and thus endolysosomal stability. Processed peptides are analyzed by mass spectrometry and abundant peptide clusters are shown to harbor T cell epitopes. The endolysosomal degradation assay has been widely used to study allergens, which are IgE-binding proteins involved in type I hypersensitivity. In this review article, we provide the first comprehensive overview of the endolysosomal degradation of 29 isoallergens and variants originating from the PR-10, Ole e 1-like, pectate lyase, defensin polyproline-linked, non-specific lipid transfer, mite group 1, 2, and 5, and tropomyosin protein families. The assay method is described in detail and suggestions for improved standardization and reproducibility are provided. The current hypothesis implies that proteins with high endolysosomal stability can induce an efficient immune response, whereas highly unstable proteins are degraded early during antigen processing and therefore not efficient for MHC II peptide presentation. To validate this concept, systematic analyses of high and low allergenic representatives of protein families should be investigated. In addition to purified molecules, allergen extracts should be degraded to analyze potential matrix effects and gastrointestinal proteolysis of food allergens. In conclusion, individual protein susceptibility and peptides obtained from the endolysosomal degradation assay are powerful tools for understanding protein immunogenicity and T cell reactivity. Systematic studies and linkage with in vivo sensitization data will allow the establishment of (machine-learning) tools to aid prediction of immunogenicity and allergenicity. The orthogonal method could in the future be used for risk assessment of novel foods and in the generation of protein-based immunotherapeutics. more...
- Published
- 2024
- Full Text
- View/download PDF
7. Identification of T cell and linear B cell epitopes on African horse sickness virus serotype 4 proteins VP1-1, VP2, VP4, VP7 and NS3.
- Author
-
Faber, Erika, van Schalkwyk, Antoinette, Ivy Tshilwane, Selaelo, Van Kleef, Mirinda, and Pretorius, Alri
- Subjects
- *
B cells , *T cells , *MONONUCLEAR leukocytes , *EPITOPES , *FOOT & mouth disease , *VIRAL proteins , *IMMUNOLOGIC memory - Abstract
• AHSV4 VP1, -2, -4, -7 and NS3 contain regions with CD8+ T cell epitopes. • Overlapping peptides spanning these AHSV4 proteins were synthesized. • Recall immune assays identified T cell and linear B cell epitopes. • Conserved T cell and linear B cell epitopes will be used in NGV. The viral proteins VP1-1, VP2, VP4, VP7 and NS3, of African horse sickness virus serotype 4 (AHSV4), have previously been identified to contain CD8+ T cell epitopes. In this study, overlapping peptides spanning the entire sequences of these AHSV4 proteins were synthesized and used to map epitopes. Peripheral blood mononuclear cells (PBMC) isolated from five horses immunized with an attenuated AHSV4 were stimulated in vitro with the synthesized peptides. Various memory immune assays were used to identify the individual peptides that contain CD8+ T cell epitopes, CD4+ T cell epitopes and linear B cell epitopes. The newly discovered individual peptides of AHSV4 proteins VP1-1, VP4, VP7 and/or NS3 that contain CD8+ T cell, CD4+ T cell or linear B cell epitopes could contribute to the design and development of new generation AHS peptide-based vaccines and therapeutics. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
8. Bioinformatic Approach of B and T Cell Epitopes of PLD and CP40 Proteins of Corynebacterium pseudotuberculosis ovis Mexican Isolate 2J-L towards a Peptide-Based Vaccine.
- Author
-
Rodríguez-Domínguez, Maria Carla, Montes-de-Oca-Jiménez, Roberto, Vázquez-Chagoyán, Juan Carlos, Rivadeneira-Barreiro, Pilar Eliana, Zambrano-Rodríguez, Pablo Cleomenes, Ruiz-Riva-Palacio, Martha Elba, Gutiérrez-Castillo, Adriana del Carmen, de-Castro-Soares, Siomar, Vieyra-Reyes, Patricia, and Arteaga-Troncoso, Gabriel more...
- Subjects
- *
CORYNEBACTERIUM pseudotuberculosis , *B cells , *EPITOPES , *T cells , *PEPTIDES , *VACCINE development , *T cell receptors - Abstract
Mapping B and T cell epitopes constitutes an important action for peptide vaccine design. PLD and CP40 virulence factors of Corynebacterium pseudotuberculosis biovar ovis, a causal agent of Caseous Lymphadenitis, have been evaluated in a murine model as good candidates for vaccine development. Therefore, the goal of this work was to in silico analyze B and T cell epitopes of the PLD and CP40 proteins of a Mexican isolate of Corynebacterium pseudotuberculosis ovis. The Immune Epitope Data Base and Resource website was employed to predict the linear and conformational B-cell, T CD4+, and T CD8+ epitopes of PLD and CP40 proteins of Corynebacterium pseudotuberculosis ovis Mexican strain 2J-L. Fifty B cell epitopes for PLD 2J-L and forty-seven for CP40 2J-L were estimated. In addition, T CD4+ and CD8+ cell epitopes were predicted for PLD 2J-L (MHC I:16 epitopes, MHC II:10 epitopes) and CP40 2J-L (MHC I: 15 epitopes, MHC II: 13 epitopes). This study provides epitopes, paying particular attention to sequences selected by different predictor programs and overlap sequences as B and T cell epitopes. PLD 2J-L and CP40 2J-L protein epitopes may aid in the design of a promising peptide-based vaccine against Caseous Lymphadenitis in Mexico. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
9. Early protective effect of a ("pan") coronavirus vaccine (PanCoVac) in Roborovski dwarf hamsters after single-low dose intranasal administration.
- Author
-
Abdelaziz, Mohammed O., Raftery, Martin J., Weihs, Julian, Bielawski, Olivia, Edel, Richard, Köppke, Julia, Vladimirova, Daria, Adler, Julia M., Firsching, Theresa, Voß, Anne, Gruber, Achim D., Hummel, Luca V., Munoz, Ivan Fernandez, Müller-Marquardt, Francesca, Willimsky, Gerald, Elleboudy, Nooran S., Trimpert, Jakob, and Schönrich, Günther more...
- Subjects
SARS-CoV-2 ,CORONAVIRUS diseases ,INTRANASAL administration ,COVID-19 vaccines ,COVID-19 ,HAMSTERS - Abstract
Introduction: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the danger posed by human coronaviruses. Rapid emergence of immunoevasive variants and waning antiviral immunity decrease the effect of the currently available vaccines, which aim at induction of neutralizing antibodies. In contrast, T cells are marginally affected by antigen evolution although they represent the major mediators of virus control and vaccine protection against virus-induced disease. Materials and Methods: We generated a multi-epitope vaccine (PanCoVac) that encodes the conserved T cell epitopes from all structural proteins of coronaviruses. PanCoVac contains elements that facilitate efficient processing and presentation of PanCoVac-encoded T cell epitopes and can be uploaded to any available vaccine platform. For proof of principle, we cloned PanCoVac into a non-integrating lentivirus vector (NILV-PanCoVac). We chose Roborovski dwarf hamsters for a first step in evaluating PanCoVac in vivo. Unlike mice, they are naturally susceptible to SARS-CoV-2 infection. Moreover, Roborovski dwarf hamsters develop COVID-19-like disease after infection with SARS-CoV-2 enabling us to look at pathology and clinical symptoms Results: Using HLA-A*0201-restricted reporter T cells and U251 cells expressing a tagged version of PanCoVac, we confirmed in vitro that PanCoVac is processed and presented by HLA-A*0201. As mucosal immunity in the respiratory tract is crucial for protection against respiratory viruses such as SARS-CoV-2, we tested the protective effect of single-low dose of NILV-PanCoVac administered via the intranasal (i.n.) route in the Roborovski dwarf hamster model of COVID-19. After infection with ancestral SARS-CoV-2, animals immunized with a single-low dose of NILV-PanCoVac i.n. did not show symptoms and had significantly decreased viral loads in the lung tissue. This protective effect was observed in the early phase (2 days post infection) after challenge and was not dependent on neutralizing antibodies. Conclusion: PanCoVac, a multi-epitope vaccine covering conserved T cell epitopes from all structural proteins of coronaviruses, might protect from severe disease caused by SARS-CoV-2 variants and future pathogenic coronaviruses. The use of (HLA-) humanized animal models will allow for further efficacy studies of PanCoVac-based vaccines in vivo. [ABSTRACT FROM AUTHOR] more...
- Published
- 2023
- Full Text
- View/download PDF
10. Design and generation of mRNAs encoding conserved regions of SARS-CoV-2 ORF1ab for T cell-mediated immune activation.
- Author
-
Nguyen, Cao Minh, Luong, Bac An, Thi Tran, Thu Thuy, Nguyen, Hoai Nghia, and Tran, Le Son
- Abstract
Aim: To generate mRNAs encoding conserved regions within SARS-CoV-2 ORF1ab which can induce strong T-cell responses to overcome the immune invasion of newly emergent variants. Methods: We selected two conserved regions with a high density of T-cell epitopes using immunoinformatics for mRNA synthesis. The ability of testing mRNAs to activate T cells for IFN-γ production was examined by an ELISpot assay and flow cytometry. Results: Two synthesized mRNAs were successfully translated in MDA-MB-231 cells and had comparable potency to the spike mRNA to induce CD4
+ and CD8+ T-cell responses in peripheral blood mononuclear cells in 29 out of 34 participants. Conclusion: This study provides a proof-of-concept for the use of SARS-CoV-2 conserved regions to develop booster vaccines capable of eliciting T-cell-mediated immunity. [ABSTRACT FROM AUTHOR] more...- Published
- 2023
- Full Text
- View/download PDF
11. iTCep: a deep learning framework for identification of T cell epitopes by harnessing fusion features.
- Author
-
Yu Zhang, Xingxing Jian, Linfeng Xu, Jingjing Zhao, Manman Lu, Yong Lin, and Lu Xie
- Subjects
DEEP learning ,T cells ,EPITOPES ,CYTOTOXIC T cells ,INTERNET servers ,PEPTIDES ,IMMUNE response ,CELL fusion - Abstract
Neoantigens recognized by cytotoxic T cells are effective targets for tumorspecific immune responses for personalized cancer immunotherapy. Quite a few neoantigen identification pipelines and computational strategies have been developed to improve the accuracy of the peptide selection process. However, these methods mainly consider the neoantigen end and ignore the interaction between peptide-TCR and the preference of each residue in TCRs, resulting in the filtered peptides often fail to truly elicit an immune response. Here, we propose a novel encoding approach for peptide-TCR representation. Subsequently, a deep learning framework, namely iTCep, was developed to predict the interactions between peptides and TCRs using fusion features derived from a feature-level fusion strategy. The iTCep achieved high predictive performance with AUC up to 0.96 on the testing dataset and above 0.86 on independent datasets, presenting better prediction performance compared with other predictors. Our results provided strong evidence that model iTCep can be a reliable and robust method for predicting TCR binding specificities of given antigen peptides. One can access the iTCep through a user-friendly web server at http://biostatistics. online/iTCep/, which supports prediction modes of peptide-TCR pairs and peptide-only. A stand-alone software program for T cell epitope prediction is also available for convenient installing at https://github.com/kbvstmd/iTCep/. [ABSTRACT FROM AUTHOR] more...
- Published
- 2023
- Full Text
- View/download PDF
12. Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometry
- Author
-
Kenji Fujiwara, Yingkuan Shao, Nan Niu, Tengyi Zhang, Brian Herbst, Mackenzie Henderson, Stephen Muth, Pingbo Zhang, and Lei Zheng
- Subjects
Pancreatic ductal adenocarcinoma ,Mass spectrometry ,T cell epitopes ,Peptidome analysis ,Immunotherapy ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Identifying T cell epitopes on pancreatic ductal adenocarcinoma (PDAC) associated antigens or neoantigens has been a challenge. In this study, we attempted to identify PDAC T cell epitopes by mass spectrometry (MS). Methods We isolated HLA class I (HLA-I) and HLA class II (HLA-II)-restricted peptides, respectively, from tissues of human PDAC by using the pan-HLA-I or pan-HLA-II affinity purification column and identified T cell epitopes by peptidome analysis with MS. Results Through peptidome analysis, we identified T cell epitopes shared by multiple patients with different HLA types and those containing sequences of both anti-HLA-I and HLA-II antibodies-affinity purified peptides. The identified epitopes bound non-matched HLA molecules and induced T cell response in peripheral T cells from both HLA-type matched and non-matched patients. Peptides containing both HLA class I and class II epitopes were able to induce polyfunctional cytokine responses in peripheral T cells. Conclusions T cell epitopes in PDAC can be discovered by the MS approach and can be designed into vaccine and TCR-T cell therapies for both HLA-type matched and non-matched patients. more...
- Published
- 2022
- Full Text
- View/download PDF
13. Early protective effect of a ('pan') coronavirus vaccine (PanCoVac) in Roborovski dwarf hamsters after single-low dose intranasal administration
- Author
-
Mohammed O. Abdelaziz, Martin J. Raftery, Julian Weihs, Olivia Bielawski, Richard Edel, Julia Köppke, Daria Vladimirova, Julia M. Adler, Theresa Firsching, Anne Voß, Achim D. Gruber, Luca V. Hummel, Ivan Fernandez Munoz, Francesca Müller-Marquardt, Gerald Willimsky, Nooran S. Elleboudy, Jakob Trimpert, and Günther Schönrich more...
- Subjects
universal COVID-19 vaccine ,coronaviruses ,multi-epitope vaccine ,T cell epitopes ,pan-coronavirus vaccine ,dwarf hamster COVID-19 model ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionThe coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the danger posed by human coronaviruses. Rapid emergence of immunoevasive variants and waning antiviral immunity decrease the effect of the currently available vaccines, which aim at induction of neutralizing antibodies. In contrast, T cells are marginally affected by antigen evolution although they represent the major mediators of virus control and vaccine protection against virus-induced disease.Materials and methodsWe generated a multi-epitope vaccine (PanCoVac) that encodes the conserved T cell epitopes from all structural proteins of coronaviruses. PanCoVac contains elements that facilitate efficient processing and presentation of PanCoVac-encoded T cell epitopes and can be uploaded to any available vaccine platform. For proof of principle, we cloned PanCoVac into a non-integrating lentivirus vector (NILV-PanCoVac). We chose Roborovski dwarf hamsters for a first step in evaluating PanCoVac in vivo. Unlike mice, they are naturally susceptible to SARS-CoV-2 infection. Moreover, Roborovski dwarf hamsters develop COVID-19-like disease after infection with SARS-CoV-2 enabling us to look at pathology and clinical symptoms.ResultsUsing HLA-A*0201-restricted reporter T cells and U251 cells expressing a tagged version of PanCoVac, we confirmed in vitro that PanCoVac is processed and presented by HLA-A*0201. As mucosal immunity in the respiratory tract is crucial for protection against respiratory viruses such as SARS-CoV-2, we tested the protective effect of single-low dose of NILV-PanCoVac administered via the intranasal (i.n.) route in the Roborovski dwarf hamster model of COVID-19. After infection with ancestral SARS-CoV-2, animals immunized with a single-low dose of NILV-PanCoVac i.n. did not show symptoms and had significantly decreased viral loads in the lung tissue. This protective effect was observed in the early phase (2 days post infection) after challenge and was not dependent on neutralizing antibodies.ConclusionPanCoVac, a multi-epitope vaccine covering conserved T cell epitopes from all structural proteins of coronaviruses, might protect from severe disease caused by SARS-CoV-2 variants and future pathogenic coronaviruses. The use of (HLA-) humanized animal models will allow for further efficacy studies of PanCoVac-based vaccines in vivo. more...
- Published
- 2023
- Full Text
- View/download PDF
14. Differential T cell immune responses to deamidated adeno-associated virus vector
- Author
-
So Jin Bing, Sune Justesen, Wells W. Wu, Abdul Mohin Sajib, Stephanee Warrington, Alan Baer, Stephan Thorgrimsen, Rong-Fong Shen, and Ronit Mazor
- Subjects
deamidation ,immunogenicity ,adeno-associated virus vector ,T cell epitopes ,gene therapy ,Genetics ,QH426-470 ,Cytology ,QH573-671 - Abstract
Despite the high safety profile demonstrated in clinical trials, the immunogenicity of adeno-associated virus (AAV)-mediated gene therapy remains a major hurdle. Specifically, T-cell-mediated immune responses to AAV vectors are related to loss of efficacy and potential liver toxicities. As post-translational modifications in T cell epitopes have the potential to affect immune reactions, the cellular immune responses to peptides derived from spontaneously deamidated AAV were investigated. Here, we report that highly deamidated sites in AAV9 contain CD4 T cell epitopes with a Th1 cytokine pattern in multiple human donors with diverse human leukocyte antigen (HLA) backgrounds. Furthermore, some peripheral blood mononuclear cell (PBMC) samples demonstrated differential T cell activation to deamidated or non-deamidated epitopes. Also, in vitro and in silico HLA binding assays showed differential binding to the deamidated or non-deamidated peptides in some HLA alleles. This study provides critical attributes to vector-immune-mediated responses, as AAV deamidation can impact the immunogenicity, safety, and efficacy of AAV-mediated gene therapy in some patients. more...
- Published
- 2022
- Full Text
- View/download PDF
15. A comprehensive study of epitopes and immune reactivity among Plasmodium species
- Author
-
Meenu Kalkal, Amit Kalkal, Sandeep Kumar Dhanda, Emily Das, Veena Pande, and Jyoti Das
- Subjects
Plasmodium ,T cell epitopes ,B cell epitopes ,Interleukin-10 (IL-10) ,Interferon-γ (IFN-γ) ,MHC-binders ,Microbiology ,QR1-502 - Abstract
Abstract Background Malaria is a life-threatening disease caused by protozoan parasite of genus Plasmodium. Various antigenic proteins of Plasmodium are considered as the major targets for the development of an effective vaccine. The aim of the current study was a comprehensive analysis of the experimentally validated epitopes of Plasmodium obtained from various immunoassays. Methods Plasmodium species epitopes were prefetched from Immune Epitope Database (IEDB). Species specific classification of available epitopes was done for both human and murine malaria parasites. Further, these T cell and B cell epitopes along with MHC I/II binders of different Plasmodium species were examined to find out their capability to induce IFN-γ and IL-10 using IFNepitope and IL-10 Pred, respectively. Results The species-specific classification of 6874 unique epitopes resulted in the selection of predominant human and murine Plasmodium species. Further, the attempt was made to analyse the immune reactivity of these epitopes for their ability to induce cytokines namely IFN-γ and IL-10. Total, 2775 epitopes were predicted to possess IFN-γ inducing ability, whereas 1275 epitopes were found to be involved in the induction of IL-10. Conclusions This study facilitates the assessment of Plasmodium epitopes and associated proteins as a potential approach to design and develop an epitope-based vaccine. Moreover, the results highlight the epitope-based immunization in malaria to induce a protective immune response. more...
- Published
- 2022
- Full Text
- View/download PDF
16. Nanoparticle Vaccine Triggers Interferon-Gamma Production and Confers Protective Immunity against Porcine Reproductive and Respiratory Syndrome Virus.
- Author
-
Sun Y, Gao Y, Su T, Zhang L, Zhou H, Zhang J, Sun H, Bai J, and Jiang P
- Abstract
The swine industry annually suffers significant economic losses caused by porcine reproductive and respiratory syndrome virus (PRRSV). Because the available commercial vaccines have limited protective efficacy against epidemic PRRSV, there is an urgent need for innovative solutions. Nanoparticle vaccines induce robust immune responses and have become a promising direction in vaccine development. In this study, we designed and produced a self-assembling nanoparticle vaccine derived from thermophilic archaeal ferritin to combat epidemic PRRSV. First, multiple T cell epitopes targeting viral structural proteins were identified by IFN-γ screening after PRRSV infection. Three different self-assembled nanoparticles with epitopes targeting viral GP3, GP4, and GP5 proteins were constructed and mixed to generate a FeCocktail vaccine. Experiments showed that the FeCocktail vaccine effectively activated CD4
+ and CD8+ T cells and effector memory T cells in mice. Piglets immunized with the FeCocktail vaccine generated specific antibodies and exhibited increased levels of PRRSV-specific IFN-γ produced by functional CD4+ and CD8+ cells. The FeCocktail also provided protective efficacy against PRRSV challenge, including mitigation of clinical symptoms, reduction of viral loads in serum and lungs, and the alleviation of lung tissue damage. In conclusion, this study offers a promising candidate vaccine for combating epidemic PRRSV, and affirms the utility of nanoparticle protein as a platform for next-generation PRRSV vaccine development. more...- Published
- 2025
- Full Text
- View/download PDF
17. Immunoinformatic approach to design T cell epitope-based chimeric vaccine targeting multiple serotypes of dengue virus.
- Author
-
Manocha N, Jha P, Kumar P, Khanna M, Chopra M, and Pai SS
- Abstract
The global dengue outbreak is a significant public health concern, with the World Health Organization recording over 3 million cases and a 0.04% case fatality rate until July 2023. The infection rate is anticipated to rise in vulnerable regions worldwide. While live-attenuated vaccines are the current standard, their effectiveness in certain populations is debated. Furthermore, the presence of four closely related dengue virus serotypes can lead to antibody-dependent enhancement, compromising vaccine efficacy. In response, we propose the development of a therapeutic subunit-vaccine based on epitopes from all four serotypes to induce robust cross-protective cellular immunity. Our approach involves designing a multi-epitope chimeric immunogen using the envelope protein of the dengue virus. MHC-I and MHC-II binding T-cell epitopes were selected based on their antigen processing criteria. The most potent and immunodominant epitopes for each serotype, considering immunogenicity, population coverage, and prediction scores, were combined using AAY linker peptides to create a stable multi-epitope polypeptide. Predicted to be both antigenic and non-allergenic, the protein design exhibits a stable and soluble tertiary structure with a half-life of 4.4 h in mammalian systems. In addition, we employed an agonist to toll-like receptor-4 at the N-terminal of the vaccine design to induce downstream immunostimulatory response, validated through docking and molecular dynamics simulations. This multi-epitope construct shows promise in eliciting an effective cellular immune response against all dengue virus serotypes. more...
- Published
- 2024
- Full Text
- View/download PDF
18. A multiepitope vaccine candidate against infectious bursal disease virus using immunoinformatics-based reverse vaccinology approach
- Author
-
Irfan Gul, Amreena Hassan, Jan Mohd Muneeb, Towseef Akram, Ehtishamul Haq, Riaz Ahmad Shah, Nazir Ahmad Ganai, Syed Mudasir Ahmad, Naveed Anjum Chikan, and Nadeem Shabir
- Subjects
IBDV ,immunoinformatics ,B cell epitopes ,T cell epitopes ,molecular dynamics simulations ,Veterinary medicine ,SF600-1100 - Abstract
Infectious bursal disease virus is the causative agent of infectious bursal disease (Gumboro disease), a highly contagious immunosuppressive disease of chicken with a substantial economic impact on small- and large-scale poultry industries worldwide. Currently, live attenuated vaccines are widely used to control the disease in chickens despite their issues with safety (immunosuppression and bursal atrophy) and efficiency (breaking through the maternally-derived antibody titer). To overcome the drawbacks, the current study has, for the first time, attempted to construct a computational model of a multiepitope based vaccine candidate against infectious bursal disease virus, which has the potential to overcome the safety and protection issues found in the existing live-attenuated vaccines. The current study used a reverse vaccinology based immunoinformatics approach to construct the vaccine candidate using major and minor capsid proteins of the virus, VP2 and VP3, respectively. The vaccine construct was composed of four CD8+ epitopes, seven CD4+ T-cell epitopes, 11 B-cell epitopes and a Cholera Toxin B adjuvant, connected using appropriate flexible peptide linkers. The vaccine construct was evaluated as antigenic with VaxiJen Score of 0.6781, immunogenic with IEDB score of 2.89887 and non-allergenic. The 55.64 kDa construct was further evaluated for its physicochemical characteristics, which revealed that it was stable with an instability index of 16.24, basic with theoretical pI of 9.24, thermostable with aliphatic index of 86.72 and hydrophilic with GRAVY score of −0.256. The docking and molecular dynamics simulation studies of the vaccine construct with Toll-like receptor-3 revealed fair structural interaction (binding affinity of −295.94 kcal/mol) and complex stability. Further, the predicted induction of antibodies and cytokines by the vaccine construct indicated the possible elicitation of the host's immune response against the virus. The work is a significant attempt to develop next-generation vaccines against the infectious bursal disease virus though further experimental studies are required to assess the efficacy and protectivity of the proposed vaccine candidate in vivo. more...
- Published
- 2023
- Full Text
- View/download PDF
19. Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometry.
- Author
-
Fujiwara, Kenji, Shao, Yingkuan, Niu, Nan, Zhang, Tengyi, Herbst, Brian, Henderson, Mackenzie, Muth, Stephen, Zhang, Pingbo, and Zheng, Lei
- Subjects
T cells ,MASS spectrometry ,EPITOPES ,PANCREATIC cancer ,HISTOCOMPATIBILITY antigens ,PANCREATIC duct - Abstract
Background: Identifying T cell epitopes on pancreatic ductal adenocarcinoma (PDAC) associated antigens or neoantigens has been a challenge. In this study, we attempted to identify PDAC T cell epitopes by mass spectrometry (MS). Methods: We isolated HLA class I (HLA-I) and HLA class II (HLA-II)-restricted peptides, respectively, from tissues of human PDAC by using the pan-HLA-I or pan-HLA-II affinity purification column and identified T cell epitopes by peptidome analysis with MS. Results: Through peptidome analysis, we identified T cell epitopes shared by multiple patients with different HLA types and those containing sequences of both anti-HLA-I and HLA-II antibodies-affinity purified peptides. The identified epitopes bound non-matched HLA molecules and induced T cell response in peripheral T cells from both HLA-type matched and non-matched patients. Peptides containing both HLA class I and class II epitopes were able to induce polyfunctional cytokine responses in peripheral T cells. Conclusions: T cell epitopes in PDAC can be discovered by the MS approach and can be designed into vaccine and TCR-T cell therapies for both HLA-type matched and non-matched patients. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
- Full Text
- View/download PDF
20. Knowledge of SARS-CoV-2 Epitopes and Population HLA Types Is Important in the Design of COVID-19 Vaccines.
- Author
-
Lani, Rafidah, Senin, Nurul Aqidah, AbuBakar, Sazaly, and Hassandarvish, Pouya
- Subjects
COVID-19 vaccines ,SARS-CoV-2 ,HLA histocompatibility antigens ,EPITOPES ,VACCINE development - Abstract
The COVID-19 pandemic has caused extensive loss of lives and economic hardship. In response, infectious disease experts and vaccine developers promptly responded by bringing forth candidate vaccines, some of which have been listed in the World Health Organization's Emergency Use Listing. Notwithstanding the diverse worldwide population genetics, the vaccines thus far developed are generic in nature for use worldwide. Differences in the human leukocyte antigen (HLA) in different populations, variation of the T cell epitopes, and the propensity of SARS-CoV-2 genetic mutations left room for improvement of the vaccines. Here, we discussed the implications of COVID-19 vaccination and SARS-CoV-2 infection by taking into consideration SARS-CoV-2 mutations, T cell epitopes, risk factors, and current platforms of candidate vaccines based on the HLA types that are commonly present in Peninsular Malaysia Chinese, Indian, and Malay populations. The HLA types associated with protection against and susceptibility to severe SARS-CoV-2 infection were identified based on reported case-control and cohort studies. The relevance of including the non-spike SARS-CoV-2 proteins in the future COVID-19 vaccines is also highlighted. This review is meant to trigger researchers to acknowledge the importance of investigating the possible relationships between the HLA haplotype and the SARS-CoV-2 strains circulating in different populations. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
- Full Text
- View/download PDF
21. Not all T cell epitopes are equally desired: a review of in silico tools for the prediction of cytokine-inducing potential of T-cell epitopes.
- Author
-
Dhanda, Sandeep Kumar, Malviya, Jitendra, and Gupta, Sudheer
- Subjects
- *
EPITOPES , *INTERNET servers , *T cells , *VACCINE effectiveness , *B cells , *IMMUNE response - Abstract
Assessment of protective or harmful T cell response induced by any antigenic epitope is important in designing any immunotherapeutic molecule. The understanding of cytokine induction potential also helps us to monitor antigen-specific cellular immune responses and rational vaccine design. The classical immunoinformatics tools served well for prediction of B cell and T cell epitopes. However, in the last decade, the prediction algorithms for T cell epitope inducing specific cytokines have also been developed and appreciated in the scientific community. This review summarizes the current status of such tools, their applications, background algorithms, their use in experimental setup and functionalities available in the tools/web servers. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
- Full Text
- View/download PDF
22. In Silico Designing of Vaccines: Methods, Tools, and Their Limitations
- Author
-
Slathia, Parvez Singh, Sharma, Preeti, and Singh, Dev Bukhsh, editor
- Published
- 2020
- Full Text
- View/download PDF
23. Identification of promising CD8 and CD4 T cell epitopes for peptide vaccine formulation against SARS-CoV-2.
- Author
-
Chakraborty, Supriyo, Deb, Bornali, Nath, Durbba, and Monoswita, Deboja
- Abstract
The novel virus “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)” has been responsible for the worldwide pandemic causing huge devastation and deaths since December 2019. The disease caused by this virus is known as COVID-19. The present study is based on immuno-informatics approach to develop a multi-epitope-loaded peptide vaccine to combat the COVID-19 menace. Here, we have reported the 9-mer CD8 T cell epitopes and 15-mer CD4 T cell epitopes, free from glycosylation sites, belonging to three proteins, viz. surface glycoprotein, membrane glycoprotein and envelope protein of this virus. Immunogenicity, aliphatic amino acid, antigenicity and hydrophilicity scores of the predicted epitopes were estimated. In addition, other physicochemical parameters, namely net charge, Boman index and amino acid contents, were also accounted. Out of all the epitopes, three CD8 T cell epitopes viz. PDPSKPSKR, DPSKPSKRS and QTQTNSPRR and three CD4 T cell epitopes viz. ASYQTQTNSPRRARS, RIGNYKLNTDHSSSS and RYRIGNYKLNTDHSS were found to be efficient targets for raising immunity in human against this virus. With the help of our identified potent epitopes, various pharma industries might initiate efforts to incorporate those epitopes with carrier protein or adjuvant to develop a multi-epitope-loaded peptide vaccine against SARS-CoV-2. The peptide vaccines are usually cost-effective and therefore, could be administered as a preventive measure to combat the spread of this disease. Proper clinical trials must be conducted prior to the use of identified epitopes as vaccine candidates. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
- Full Text
- View/download PDF
24. Design of Vaccine Targeting Zika Virus Polyprotein by Immunoinformatics Technique.
- Author
-
Dixit, Neeraj Kumar
- Abstract
Malformation and microcephaly cases in neonates have increased dramatically as the prevalence of ZIKV infection has increased, implying congenital transmission. With the use of in-silico tools epitopes of B and T cell were used to look at polyproteins. We selected 82 CD8 and 87 CD4 T cell epitopes considering different parameters such as different HLA alleles that bind to the epitopes, with immunogenicity. SVMT triv lenear B cell prediction was used to look at poly proteins in order to predict 10 high scoring B cell epitopes. All epitopes are predicted to be antigenic, non-allergenic and stable. According to the author of this work, MHC I HLA-A*68:01, HLA-B*15:25, and HLA-A*01:01 include structures that bind to epitopes QVASAGITYTDR, TPAVQHAVTTSY, and PRTGLDFSDLYY choose by higher negative Docking score. For MHC II HLA-DRB1*07:01, which binds both PKKKSGGFRIVN and KKKSGGFRIVNM epitopes, a high negative value was chosen in accordance. WRLKRAHLIE, LGLTAVRLVD, and LETIMLLGLL are B cell epitopes that have been detected and identified as adequate epitopes against ZIKV. Finally, we developed an in-silico universal vaccine that is expected to elicit broad further in vivo testing. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
- Full Text
- View/download PDF
25. COVID-19 coronavirus vaccine T cell epitope prediction analysis based on distributions of HLA class I loci (HLA-A, -B, -C) across global populations
- Author
-
Yina Cun, Chuanyin Li, Lei Shi, Ming Sun, Shuying Dai, Le Sun, Li Shi, and Yufeng Yao
- Subjects
sars-cov-2 ,human leukocyte antigen (hla) ,t cell epitopes ,population coverage ,vaccine ,Immunologic diseases. Allergy ,RC581-607 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
T cell immunity, such as CD4 and/or CD8 T cell responses, plays a vital role in controlling the virus infection and pathological damage. Several studies have reported SARS-CoV-2 proteins could serve as ideal vaccine candidates against SARS-CoV-2 infection by activating the T cell responses. In the current study, based on the SARS-CoV-2 sequence and distribution of host human leukocyte antigen (HLA), we predicted the possible epitopes for the vaccine against SARS-CoV-2 infections. Firstly, the current study retrieved the SARS-CoV-2 S and N protein sequences from the NCBI Database. Then, using the Immune Epitope Database Analysis Resource, we predicted the CTL epitopes of the SARS-CoV-2 S and N proteins according to worldwide frequency distributions of HLA-A, -B, and -C alleles (>1%). Our results predicted 90 and 106 epitopes of N and S proteins, respectively. Epitope cluster analysis showed 16 and 34 respective clusters of SARS-CoV-2 N and S proteins, which covered 95.91% and 96.14% of the global population, respectively. After epitope conservancy analysis, 8 N protein epitopes and 6 S protein epitopes showed conservancy within two SARS-CoV-2 types. Of these 14 epitopes, 13 could cover SARS coronavirus and Bat SARS-like coronavirus. The remaining epitope (KWPWYIWLGF1211-1220) could cover MERS coronavirus. Finally, the 14-epitope combination could vaccinate 89.60% of all individuals worldwide. Our results propose single or combined CTL epitopes predicted in the current study as candidates for vaccines to effectively control SARS-CoV-2 infection and development. more...
- Published
- 2021
- Full Text
- View/download PDF
26. Norovirus-Specific CD8+ T Cell Responses in Human Blood and TissuesSummary
- Author
-
Ajinkya Pattekar, Lena S. Mayer, Chi Wai Lau, Chengyang Liu, Olesya Palko, Meenakshi Bewtra, HPAP Consortium, Lisa C. Lindesmith, Paul D. Brewer-Jensen, Ralph S. Baric, Michael R. Betts, Ali Naji, E. John Wherry, and Vesselin T. Tomov more...
- Subjects
T Cell Epitopes ,Norovirus-Specific T Cells ,Norovirus Tetramers ,Norovirus TRM ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Noroviruses (NoVs) are the leading cause of acute gastroenteritis worldwide and are associated with significant morbidity and mortality. Moreover, an asymptomatic carrier state can persist following acute infection, promoting NoV spread and evolution. Thus, defining immune correlates of NoV protection and persistence is needed to guide the development of future vaccines and limit viral spread. Whereas antibody responses following NoV infection or vaccination have been studied extensively, cellular immunity has received less attention. Data from the mouse NoV model suggest that T cells are critical for preventing persistence and achieving viral clearance, but little is known about NoV-specific T-cell immunity in humans, particularly at mucosal sites. Methods: We screened peripheral blood mononuclear cells from 3 volunteers with an overlapping NoV peptide library. We then used HLA-peptide tetramers to track virus-specific CD8+ T cells in peripheral, lymphoid, and intestinal tissues. Tetramer+ cells were further characterized using markers for cellular trafficking, exhaustion, cytotoxicity, and proliferation. Results: We defined 7 HLA-restricted immunodominant class I epitopes that were highly conserved across pandemic strains from genogroup II.4. NoV-specific CD8+ T cells with central, effector, or tissue-resident memory phenotypes were present at all sites and were especially abundant in the intestinal lamina propria. The properties and differentiation states of tetramer+ cells varied across donors and epitopes. Conclusions: Our findings are an important step toward defining the breadth, distribution, and properties of human NoV T-cell immunity. Moreover, the molecular tools we have developed can be used to evaluate future vaccines and engineer novel cellular therapeutics. more...
- Published
- 2021
- Full Text
- View/download PDF
27. A comprehensive study of epitopes and immune reactivity among Plasmodium species.
- Author
-
Kalkal, Meenu, Kalkal, Amit, Dhanda, Sandeep Kumar, Das, Emily, Pande, Veena, and Das, Jyoti
- Subjects
EPITOPES ,PLASMODIUM ,B cells ,VACCINE effectiveness ,PROTOZOAN diseases ,SPECIES - Abstract
Background: Malaria is a life-threatening disease caused by protozoan parasite of genus Plasmodium. Various antigenic proteins of Plasmodium are considered as the major targets for the development of an effective vaccine. The aim of the current study was a comprehensive analysis of the experimentally validated epitopes of Plasmodium obtained from various immunoassays. Methods: Plasmodium species epitopes were prefetched from Immune Epitope Database (IEDB). Species specific classification of available epitopes was done for both human and murine malaria parasites. Further, these T cell and B cell epitopes along with MHC I/II binders of different Plasmodium species were examined to find out their capability to induce IFN-γ and IL-10 using IFNepitope and IL-10 Pred, respectively. Results: The species-specific classification of 6874 unique epitopes resulted in the selection of predominant human and murine Plasmodium species. Further, the attempt was made to analyse the immune reactivity of these epitopes for their ability to induce cytokines namely IFN-γ and IL-10. Total, 2775 epitopes were predicted to possess IFN-γ inducing ability, whereas 1275 epitopes were found to be involved in the induction of IL-10. Conclusions: This study facilitates the assessment of Plasmodium epitopes and associated proteins as a potential approach to design and develop an epitope-based vaccine. Moreover, the results highlight the epitope-based immunization in malaria to induce a protective immune response. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
- Full Text
- View/download PDF
28. The interdependence of machine learning and LC-MS approaches for an unbiased understanding of the cellular immunopeptidome.
- Author
-
Nielsen, Morten, Ternette, Nicola, and Barra, Carolina
- Abstract
The comprehensive collection of peptides presented by major histocompatibility complex (MHC) molecules on the cell surface is collectively known as the immunopeptidome. The analysis and interpretation of such data sets holds great promise for furthering our understanding of basic immunology and adaptive immune activation and regulation, and for direct rational discovery of T cell antigens and the design of T-cell-based therapeutics and vaccines. These applications are, however, challenged by the complex nature of immunopeptidome data. Here, we describe the benefits and shortcomings of applying liquid chromatography-tandem mass spectrometry (MS) to obtain large-scale immunopeptidome data sets and illustrate how the accurate analysis and optimal interpretation of such data is reliant on the availability of refined and highly optimized machine learning approaches. Further, we demonstrate how the accuracy of immunoinformatics prediction methods within the field of MHC antigen presentation has benefited greatly from the availability of MS-immunopeptidomics data, and exemplify how optimal antigen discovery is best performed in a synergistic combination of MS experiments and such in silico models trained on large-scale immunopeptidomics data. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
- Full Text
- View/download PDF
29. In silico identification and modification of T cell epitopes in pertussis antigens associated with tolerance
- Author
-
Corine Kruiswijk, Guilhem Richard, Merijn L.M. Salverda, Pooja Hindocha, William D. Martin, Anne S. De Groot, and Elly Van Riet
- Subjects
pertussis ,omv ,vaccine ,hla class ii ,t cell epitopes ,tolerance ,immunoinformatics ,epimatrix ,janusmatrix ,Immunologic diseases. Allergy ,RC581-607 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The resurgence of whooping cough since the introduction of acellular (protein) vaccines has led to a renewed interest in the development of improved pertussis vaccines; Outer Membrane Vesicles (OMVs) carrying pertussis antigens have emerged as viable candidates. An in silico immunogenicity screen was carried out on 49 well-known Bordetella pertussis proteins in order to better understand their potential role toward the efficacy of pertussis OMVs for vaccine design; seven proteins were identified as being good candidates for including in optimized cellular and acellular pertussis vaccines. We then screened these antigens for putative tolerance-inducing sequences, as proteins with reduced tolerogenicity have improved vaccine potency in preclinical models. We used specialized homology tools (JanusMatrix) to identify peptides in the proteins that were cross-reactive with human sequences. Four of the 19 identified cross-reactive peptides were detolerized in silico using a separate tool, OptiMatrix, which disrupted the potential of these peptides to bind to human HLA and murine MHC. Four selected cross-reactive peptides and their detolerized variants were synthesized and their binding to a set of eight common HLA class II alleles was assessed in vitro. Reduced binding affinity to HLA class II was observed for the detolerized variants compared to the wild-type peptides, highlighting the potential of this approach for designing more efficacious pertussis vaccines. more...
- Published
- 2020
- Full Text
- View/download PDF
30. Development of Hypoallergenic Derivatives of Cra a 1 with B Cell Epitope Deletion and T Cell Epitope Retention.
- Author
-
Huan F, Gao S, Ni LN, Wu MX, Gu Y, Yun X, Liu M, Lai D, Xiao AF, and Liu GM
- Subjects
- Animals, Mice, Tropomyosin immunology, Tropomyosin genetics, Tropomyosin chemistry, Mice, Inbred BALB C, Female, Humans, Cell Proliferation drug effects, CD4-Positive T-Lymphocytes immunology, Shellfish Hypersensitivity immunology, T-Lymphocytes immunology, T-Lymphocytes drug effects, Epitopes, T-Lymphocyte immunology, Epitopes, T-Lymphocyte chemistry, Epitopes, T-Lymphocyte genetics, Allergens immunology, Allergens chemistry, Allergens genetics, Epitopes, B-Lymphocyte immunology, Epitopes, B-Lymphocyte chemistry, Epitopes, B-Lymphocyte genetics, Crassostrea immunology, Crassostrea chemistry, Crassostrea genetics
- Abstract
Tropomyosin was reported as an important allergen in Crassostrea angulata and designated as Cra a 1. The localization of the T cell epitopes and the reduction of the immunoreactivity of Cra a 1 are still lacking. In this study, four T cell epitopes were identified by using wild-type Cra a 1 (wtCra a 1)-immunized mouse splenocytes cultured with synthetic peptides. The immunoreactivity was maintained after chemical denaturation treatment, indicating that the linear epitope is an immunodominant epitope of wtCra a 1. Furthermore, the hypoallergenic derivative (mCra a 1) was developed by the deletion of linear B cell epitopes and retention of T cell epitopes. mCra a 1 could stimulate CD4
+ T cell proliferation and upregulate interleukin-10 secretion. Overall, basophil activation by mCra a 1 was low, but its ability to induce T cell proliferation was retained, suggesting that mCra a 1 may serve as a viable candidate for treating oyster allergy. more...- Published
- 2024
- Full Text
- View/download PDF
31. In silico Design and Characterization of Multi-epitopes Vaccine for SARS-CoV2 from Its Spike Protein.
- Author
-
Kathwate, Gunderao H.
- Abstract
COVID 19 is a disease caused by a novel coronavirus, SARS-CoV2 originated in China most probably of Bat origin. Multiepitopes vaccine would be useful in eliminating SARS-CoV2 infections as asymptomatic patients are in large numbers. In response to this, we utilized bioinformatic tools to develop an efficient vaccine candidate against SARS-CoV2. The designed vaccine has effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Predicted BCR and TCR epitopes found antigenic, non-toxic and probably non-allergen. Modeled and the refined tertiary structure predicted as valid for further use. Protein–Protein interaction prediction of TLR2/4 and designed vaccine indicates promising binding. The designed multiepitope vaccine has induced cell-mediated and humoral immunity along with increased interferon-gamma response. Macrophages and dendritic cells were also found to increase upon the vaccine exposure. In silico codon optimization and cloning in expression vector indicates that the vaccine can be efficiently expressed in E. coli. In conclusion, the predicted vaccine is a good antigen, probable no allergen, and has the potential to induce cellular and humoral immunity. [ABSTRACT FROM AUTHOR] more...
- Published
- 2022
- Full Text
- View/download PDF
32. Construction and immunogenicity of a T cell epitope-based subunit vaccine candidate against Mycobacterium tuberculosis.
- Author
-
Fan, Xueting, Li, Xiaoyan, Wan, Kanglin, Zhao, Xiuqin, Deng, Yunli, Chen, Zixin, Luan, Xiuli, Lu, Shuangshuang, and Liu, Haican
- Subjects
- *
MYCOBACTERIUM tuberculosis , *T cells , *TUBERCULOSIS , *TUBERCULOSIS vaccines , *RECOMBINANT proteins , *IMMUNOGLOBULIN G , *CELLULAR inclusions , *ANTIBODY formation - Abstract
• This study is the first to design a tuberculosis vaccine based on T cell epitopes. • T cell epitope-based subunit vaccinestimulated strong Th1-type cellular immune response. • The used approach could be useful against latent TB. Despite antibiotic treatment and Bacille Calmette-Guérin (BCG) vaccination, Mycobacterium tuberculosis remains a major public health burden in most developing countries. Therefore, developing an improved vaccine is high priority. In this study, we cloned the genes of the immunodominant antigen of M. tuberculosis viz. its 38-kDa antigen (Pst homolog) (Rv0934, PstS1), and its T cell epitopes (amino acid [aa]169–405 and [aa]802–1119), which we termed PstS1p. Prokaryotic expression showed that the two recombinant proteins were mainly in the form of inclusion bodies. We also evaluated the immunity and immunogenicity of PstS1 and PstS1p. Both PstS1 and its T cell epitopes elicited significantly higher antigen-specific immunoglobulin G (IgG) antibodies in mouse serum, indicating that they enhanced antibody response. They also elicited the T helper 1 (Th1)-type response and promoted CD4+ T cell proliferation. Compared to PstS1, PstS1p promoted stronger cell-mediated immune response. These data indicate that PstS1p is highly immunogenic in mice, and may be a promising candidate vaccine for controlling tuberculosis. [ABSTRACT FROM AUTHOR] more...
- Published
- 2021
- Full Text
- View/download PDF
33. NetMHCphosPan - Pan-specific prediction of MHC class I antigen presentation of phosphorylated ligands
- Author
-
Carina Thusgaard Refsgaard, Carolina Barra, Xu Peng, Nicola Ternette, and Morten Nielsen
- Subjects
MHC antigen presentation ,Phosphorylation ,Motif deconvolution ,T cell epitopes ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Post-translational modifications of proteins play a crucial part in carcinogenesis. Phosphorylated peptides have shown to be presented by MHC class I molecules and recognised by cytotoxic T cells, making them a promising target for immunotherapy. Identification of phosphorylated MHC class I ligands has so far predominantly been done using bioinformatic tools trained on unmodified peptides. Only one tool, PhosMHCpred, has been developed specifically for the prediction of phosphorylated MHC class I ligands so far and this tool has been trained only on a limited number of alleles and provides a limited peptide length coverage (only including 9-mers).Here we propose a method, termed NetMHCphosPan, for the prediction of MHC presented phosphopeptides. The method is trained using the NNAlign_MA framework, which allows incorporating mixed data types and information leverage between data sets resulting in a greatly improved MHC and peptide length coverage and an overall increased predictive power compared to PhosMHCpred. Motif deconvolution suggested a strong preference for phosphosites to be located in position 4 of the binding motif, and enrichment of proline at P5 and arginine at P1. The improved performance, driven by the extended length and allelic coverage, of NetMHCphosPan over current state-of-the-art methods, was further validated on a large benchmark data set independent from the model development.In conclusion, we have confirmed the high power of NNAlign_MA for motif deconvolution of complex immuno-peptidomics data and have developed a novel method for prediction of MHC presented phosphopeptides with improved predictive power and a broader peptide length and MHC coverage compared to current state-of-the-art methods. The developed method is available at http://www.cbs.dtu.dk/services/NetMHCphosPan-1.0. more...
- Published
- 2021
- Full Text
- View/download PDF
34. Immunogenic T cell epitopes of SARS-CoV-2 are recognized by circulating memory and naïve CD8 T cells of unexposed individuals
- Author
-
Isaac Quiros-Fernandez, Mansour Poorebrahim, Elham Fakhr, and Angel Cid-Arregui
- Subjects
SARS-CoV-2 ,COVID-19 ,T cell epitopes ,pre-existing cross-reactivity ,CD8 memory T cells ,immunotherapy ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: Recent studies have provided evidence of T cell reactivity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in significant numbers of non-infected individuals, which has been attributed to cross-reactive CD4 memory T cells from previous exposure to seasonal coronaviruses. Less evidence of cross-reactive memory CD8 T cells has been documented to date. Methods: We used the NetCTLPan neural network of the Epitope Database and Analysis Resource to select a series of 27 HLA-A*02:01 epitopes derived from the proteome of SARS-CoV-2. Their binding capacity was assessed by a HLA-A*02:01 stabilization assay and by quantifying their binding to HLA-A*02:01 monomers for the generation of tetramers. Their ability to stimulate and induce expansion of SARS-CoV-2 reactive CD8 T cells was measured by flow cytometry. The TCR repertoire of COVID convalescent and healthy unexposed donors was analysed using the MIRA database. Findings: The HLA-A*02:01 epitopes tested were able to stabilise HLA molecules and induce activation of CD8 T cells of healthy unexposed donors. Our results, based on specific tetramer binding, provide evidence supporting the presence of frequent cross-reactive CD8 T cells to SARS-CoV-2 antigens in non-exposed individuals. Interestingly, the reactive cells were distributed into naïve, memory and effector subsets. Interpretation: Our data are consistent with a significant proportion of the reactive CD8 T clones belonging to the public shared repertoire, readily available in absence of previous contact with closely related coronaviruses. Furthermore, we demonstrate the immunogenic capacity of long peptides carrying T cell epitopes, which can serve to isolate virus-specific T cell receptors among the ample repertoire of healthy unexposed subjects and could have application in COVID-19 immunotherapy. Limitations of our study are that it concentrated on one MHC I allele (HLA-A*02:01) and the low numbers of samples and epitopes tested. Funding: See the Acknowledgements section. more...
- Published
- 2021
- Full Text
- View/download PDF
35. Impact of in vitro evolution on antigenic diversity of Mycobacterium bovis bacillus Calmette-Guerin (BCG)
- Author
-
Copin, Richard, Coscollá, Mireia, Efstathiadis, Efstratios, Gagneux, Sebastien, and Ernst, Joel D
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Prevention ,Tuberculosis Vaccine ,Infectious Diseases ,Rare Diseases ,Immunization ,Tuberculosis ,Biotechnology ,Vaccine Related ,Infection ,Good Health and Well Being ,Amino Acid Substitution ,Antigenic Variation ,BCG Vaccine ,DNA Copy Number Variations ,Epitopes ,T-Lymphocyte ,Evolution ,Molecular ,Genome ,Bacterial ,Humans ,Mycobacterium bovis ,Phylogeny ,Selection ,Genetic ,Mycobacterium bovis bacillus ,Calmette-Guerin ,In vitro evolution ,Phylogenetic diversity ,T cell epitopes ,Mycobacterium bovis bacillus Calmette-Guerin ,Biological Sciences ,Agricultural and Veterinary Sciences ,Medical and Health Sciences ,Virology ,Biomedical and clinical sciences ,Health sciences - Abstract
Mycobacterium bovis bacillus Calmette-Guerin (BCG), the only vaccine currently used against tuberculosis, is an attenuated derivative of M. bovis that has been propagated in vitro for more than 40 years. We have previously reported that the experimentally-verified human T cell epitopes of the M. tuberculosis complex (MTBC) are the most conserved elements of the genome; whether immune recognition is the force driving the conservation of epitopes in the MTBC is unknown. Therefore, we sequenced the genomes of 12 BCG strains to determine whether T cell epitopes were under selection pressure during BCG in vitro evolution. We constructed a genome-wide phylogeny and refined the previously-determined BCG phylogeny. Notably, we identified a new cluster between BCG Japan and BCG Russia, and repositioned the relationships of several strains within the lineage. We also compared the sequence diversity of 1530 experimentally verified human T cell epitopes in the BCG vaccines with those in the MTBC. We found 23% of the known T cell epitopes are absent, and that the majority (82%) of the absent epitopes in BCG are contained in 6 proteins encoded in 2 regions of difference (RD) unique to BCG strains. We also found that T cell epitope sequences in BCG are more conserved than non-epitope sequences in the same gene. Finally, we find evidence that epitope sequence variation in BCG potentially affects human T cell recognition. These findings provide new insight into sequence variation in a slow-growing bacterium closely related to the MTBC that has been subjected to prolonged passage outside of a mammalian host, and indicate little difference in the extent of variation in vivo and in vitro. more...
- Published
- 2014
36. Knowledge of SARS-CoV-2 Epitopes and Population HLA Types Is Important in the Design of COVID-19 Vaccines
- Author
-
Rafidah Lani, Nurul Aqidah Senin, Sazaly AbuBakar, and Pouya Hassandarvish
- Subjects
infectious diseases ,SARS-CoV-2 ,COVID-19 ,vaccine ,T cell epitopes ,human leukocyte antigens ,Medicine - Abstract
The COVID-19 pandemic has caused extensive loss of lives and economic hardship. In response, infectious disease experts and vaccine developers promptly responded by bringing forth candidate vaccines, some of which have been listed in the World Health Organization’s Emergency Use Listing. Notwithstanding the diverse worldwide population genetics, the vaccines thus far developed are generic in nature for use worldwide. Differences in the human leukocyte antigen (HLA) in different populations, variation of the T cell epitopes, and the propensity of SARS-CoV-2 genetic mutations left room for improvement of the vaccines. Here, we discussed the implications of COVID-19 vaccination and SARS-CoV-2 infection by taking into consideration SARS-CoV-2 mutations, T cell epitopes, risk factors, and current platforms of candidate vaccines based on the HLA types that are commonly present in Peninsular Malaysia Chinese, Indian, and Malay populations. The HLA types associated with protection against and susceptibility to severe SARS-CoV-2 infection were identified based on reported case-control and cohort studies. The relevance of including the non-spike SARS-CoV-2 proteins in the future COVID-19 vaccines is also highlighted. This review is meant to trigger researchers to acknowledge the importance of investigating the possible relationships between the HLA haplotype and the SARS-CoV-2 strains circulating in different populations. more...
- Published
- 2022
- Full Text
- View/download PDF
37. Design of Epitope Based Vaccine for Dengue Virus Using Immunoinformatic Approach.
- Author
-
Dixit, Neeraj Kumar and Kumar, Anup
- Subjects
- *
DENGUE viruses , *VIRAL vaccines , *ARBOVIRUS diseases , *MOLECULAR docking , *VIRAL proteins , *T cells , *MOSQUITOES - Abstract
Dengue is an infectious disease caused by one of the four serotypes of the dengue virus. It is a mosquito borne disease and the female Aedes mosquito is mainly spread to humans. The disease exists mostly in tropical and subtropical areas, placing about a third of the human population at risk of infection worldwide. The tremendous variety and the minimal similarity in identity at the level of amino acids contribute to a troublesome obstacle in the production of an effective vaccine. Vaccine production has been oriented towards the rational design of the epitope based vaccine through available immunological evidence, the advancement of the antigenic peptide prediction method, and the integration of molecular docking into immunoinformatics. So we are discovering new prevention steps, using immunoinformatics methods to create dengue epitope based subunit vaccine that can produce different immune responses inside the host. For structural and non-structural dengue virus proteins, distinct B and T cell binding epitopes were expected. Microscopic interactions between the epitope and the allele were confirmed by molecular docking. In this work epitopes KRSGIQEVD, RRDLRLAAN, RRGDLPVWL, FQIYKRSGI and THSSAAQRRGRIGRNP were predicted as a new immunotherapeutic agent for dengue vaccine that can provide prevention and control of outbreaks. [ABSTRACT FROM AUTHOR] more...
- Published
- 2021
- Full Text
- View/download PDF
38. Immunoinformatics Approach for the Identification and Characterization of T Cell and B Cell Epitopes towards the Peptide-Based Vaccine against SARS-CoV-2.
- Author
-
Chakraborty, Chiranjib, Sharma, Ashish Ranjan, Bhattacharya, Manojit, Sharma, Garima, and Lee, Sang-Soo
- Subjects
- *
B cells , *T cells , *SARS-CoV-2 , *EPITOPES , *VACCINE development - Abstract
• We discussed immunoinformatics approaches for SARS-CoV-2 vaccine development. • Different topics such as T cell and B cell epitopes, their identification and characterization for vaccine development against SARS-CoV-2 were discussed. • We also summarize a variety of infectious pathogens and diseases where immunoinformatics studies were applied. • Different immunoinformatics tools were enlisted for SARS-CoV-2 vaccine development. Presently, immunoinformatics is playing a significant role in epitope identification and vaccine designing for various critical diseases. Using immunoinformatics, several scientists are trying to identify and characterize T cell and B cell epitopes as well as design peptide-based vaccine against SARS-CoV-2. In this review article, we have tried to discuss the importance in adaptive immunity and its significance for designing the SARS-CoV-2 vaccine. Moreover, we have attempted to illustrate several significant key points for utilizing immunoinformatics for vaccine designing, such as the criteria for selection and identification of epitopes, T cell epitope, and B cell epitope prediction and different emerging tools/databases for immunoinformatics. In the current scenario, a few immunoinformatics studies have been performed for various infectious pathogens and related diseases. Thus, we have also summarized and included these current immunoinformatics studies in this review article. Finally, we have discussed about the probable T cell and B cell epitopes and their identification and characterization for vaccine designing against SARS-CoV-2. [ABSTRACT FROM AUTHOR] more...
- Published
- 2021
- Full Text
- View/download PDF
39. Immunological and Symptomatic Effects of Oral Intake of Transgenic Rice Containing 7 Linked Major T-Cell Epitopes from Japanese Cedar Pollen Allergens.
- Author
-
Endo, Tomonori, Asaka, Daiya, Nakayama, Tsuguhisa, Saito, Shota, Kodama, Hiroki, Mitsuyoshi, Ryoto, Takaishi, Shinya, Sugimoto, Naoki, Omae, Sachiko, Takagi, Hidenori, Wakasa, Yuhya, Ozawa, Kenjiro, Takano, Makoto, Takaiwa, Fumio, Kojima, Hiromi, and Saito, Saburo more...
- Subjects
- *
TRANSGENIC rice , *CRYPTOMERIA japonica , *EPITOPES , *ALLERGENS , *POLLEN , *RICE quality , *RICE diseases & pests - Abstract
Background: A rice-based peptide vaccine containing 7 linked human predominant T-cell epitopes (7Crp) derived from Japanese cedar (JC) pollen allergens, Cry j 1 and Cry j 2, was developed. Here, we examined the efficacy and safety of this transgenic rice in JC pollinosis patients. Methods: Transgenic rice (5, 20, and 80 g) was administered orally. We measured the T-cell proliferative activity against 7Crp, Cry j 1, and Cry j 2; the cytokine expression levels; and specific IgE and IgG4 production levels. In addition, the symptom and medication scores were monitored during the pollen season, and quality of life (QOL) was evaluated. Results: T-cell proliferative activities to Cry j 1, Cry j 2, and 7Crp were significantly depressed in a dose-dependent manner. Oral intake of 80 g transgenic rice for 20 weeks resulted in significant suppression of allergen-specific T-cell proliferation with downregulation of IL-13 and upregulation of IL-10 levels but no changes to specific IgE and IgG4 levels. The QOL symptom scores for allergic rhinitis were not significantly improved. Conclusions: Allergen-specific T-cell responses were significantly reduced by oral intake of transgenic rice in a dose-dependent manner. However, neither medication score nor QOL symptom scores could be improved during the JC pollen season with oral intake of transgenic rice for 20 weeks. [ABSTRACT FROM AUTHOR] more...
- Published
- 2021
- Full Text
- View/download PDF
40. Influenza Virus-Derived CD8 T Cell Epitopes: Implications for the Development of Universal Influenza Vaccines.
- Author
-
Kim SH, Españo E, Padasas BT, Son JH, Oh J, Webby RJ, Lee YR, Park CS, and Kim JK
- Abstract
The influenza virus poses a global health burden. Currently, an annual vaccine is used to reduce influenza virus-associated morbidity and mortality. Most influenza vaccines have been developed to elicit neutralizing Abs against influenza virus. These Abs primarily target immunodominant epitopes derived from hemagglutinin (HA) or neuraminidase (NA) of the influenza virus incorporated in vaccines. However, HA and NA are highly variable proteins that are prone to antigenic changes, which can reduce vaccine efficacy. Therefore, it is essential to develop universal vaccines that target immunodominant epitopes derived from conserved regions of the influenza virus, enabling cross-protection among different virus variants. The internal proteins of the influenza virus serve as ideal targets for universal vaccines. These internal proteins are presented by MHC class I molecules on Ag-presenting cells, such as dendritic cells, and recognized by CD8 T cells, which elicit CD8 T cell responses, reducing the likelihood of disease and influenza viral spread by inducing virus-infected cell apoptosis. In this review, we highlight the importance of CD8 T cell-mediated immunity against influenza viruses and that of viral epitopes for developing CD8 T cell-based influenza vaccines., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2024. The Korean Association of Immunologists.) more...
- Published
- 2024
- Full Text
- View/download PDF
41. Immunogenicity risk assessment for biotherapeutics through in vitro detection of CD134 and CD137 on T helper cells
- Author
-
Sivan Cohen, Srividya Myneni, Anna Batt, Joyce Guerrero, Jochen Brumm, and Shan Chung
- Subjects
Immunogenicity ,biotherapeutics ,CD134 ,CD137 ,T cell epitopes ,T cell activation ,Therapeutics. Pharmacology ,RM1-950 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Biotherapeutics, which are biologic medications that are natural or bioengineered products of living cells, have revolutionized the treatment of many diseases. However, unwanted immune responses still present a major challenge to their widespread adoption. Many patients treated with biotherapeutics develop antigen-specific anti-drug antibodies (ADAs) that may reduce the efficacy of the therapy or cross-react with the endogenous counterpart of a protein therapeutic, or both. Here, we describe an in vitro method for assessing the immunogenic risk of a biotherapeutic. We found a correlation between clinical immunogenicity and the frequency with which a biotherapeutic stimulated an increase in CD134, CD137, or both cell surface markers on CD4+ T cells. Using high-throughput flow cytometry, we examined the effects of 14 biotherapeutics with diverse rates of clinical immunogenicity on peripheral blood mononuclear cells from 120 donors with diverse human leukocyte antigen class II-encoding alleles. Biotherapeutics with high rates of ADA development in the clinic had higher proportions of CD4+ T cells positive for CD134 or CD137 than biotherapeutics with low clinical immunogenicity. This method provides a rapid and simple preclinical test of the immunogenic potential of a new candidate biotherapeutic or biosimilar. Implementation of this approach during biotherapeutic research and development enables rapid elimination of candidates that are likely to cause ADA-related adverse events and detrimental consequences. more...
- Published
- 2021
- Full Text
- View/download PDF
42. Designing of cytotoxic and helper T cell epitope map provides insights into the highly contagious nature of the pandemic novel coronavirus SARS-CoV-2
- Author
-
Seema Mishra
- Subjects
SARS-CoV-2 ,SARS-CoV-2 proteome ,T cell epitopes ,immunoinformatics ,immunopathology ,cytokine storm ,Science - Abstract
Novel coronavirus, SARS-CoV-2, has emerged as one of the deadliest pathogens of this century, creating an unprecedented pandemic. Belonging to the betacoronavirus family, it primarily spreads through human contact via symptomatic and asymptomatic transmission. Despite several attempts since it emerged, there is no known treatment in the form of drugs or vaccines. Hence, work on developing a potential multi-subunit vaccine is the need of the hour. In this study, attempts have been made to find globally conserved epitopes from the entire set of SARS-CoV-2 proteins as there is as yet, no clear information on the immunogenicity of these proteins. Using diverse computational tools, a ranked list of probable immunogenic, promiscuous epitopes generated through all the three main stages of antigen processing and presentation pathways has been prioritized. Moreover, several useful insights were gleaned during these analyses. One of the most important insights is that all of the proteins in this pathogen present unique epitopes, so that the targeting of a few specific viral proteins is not likely to result in an effective immune response in humans. Due to the presence of these unique epitopes in all of the SARS-CoV-2 proteins, stronger immune responses generated by T cell hyperactivation may lead to cytokine storm and immunopathology and consequently, remote chances of human survival. These epitopes, after due validation in vitro, may thus need to be presented to the human body in that form of multi-subunit epitope-based vaccine that avoids such immunopathologies. more...
- Published
- 2020
- Full Text
- View/download PDF
43. Immunogenicity of Immunotoxins Containing Pseudomonas Exotoxin A: Causes, Consequences, and Mitigation
- Author
-
Ronit Mazor and Ira Pastan
- Subjects
recombinant immunotoxins ,neutralizing antibodies ,anti-drug antibodies (ADA) ,B cell epitopes ,T cell epitopes ,moxetumomab pasudotox ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Immunotoxins are cytolytic fusion proteins developed for cancer therapy, composed of an antibody fragment that binds to a cancer cell and a protein toxin fragment that kills the cell. Pseudomonas exotoxin A (PE) is a potent toxin that is used for the killing moiety in many immunotoxins. Moxetumomab Pasudotox (Lumoxiti) contains an anti-CD22 Fv and a 38 kDa portion of PE. Lumoxiti was discovered in the Laboratory of Molecular Biology at the U.S. National Cancer Institute and co-developed with Medimmune/AstraZeneca to treat hairy cell leukemia. In 2018 Lumoxiti was approved by the US Food and Drug Administration for the treatment of drug-resistant Hairy Cell Leukemia. Due to the bacterial origin of the killing moiety, immunotoxins containing PE are highly immunogenic in patients with normal immune systems, but less immunogenic in patients with hematologic malignancies, whose immune systems are often compromised. LMB-100 is a de-immunized variant of the toxin with a humanized antibody that targets mesothelin and a PE toxin that was rationally designed for diminished reactivity with antibodies and B cell receptors. It is now being evaluated in clinical trials for the treatment of mesothelioma and pancreatic cancer and is showing somewhat diminished immunogenicity compared to its un modified parental counterpart. Here we review the immunogenicity of the original and de-immunized PE immunotoxins in mice and patients, the development of anti-drug antibodies (ADAs), their impact on drug availability and their effect on clinical efficacy. Efforts to mitigate the immunogenicity of immunotoxins and its impact on immunogenicity will be described including rational design to identify, remove, or suppress B cell or T cell epitopes, and combination of immunotoxins with immune modulating drugs. more...
- Published
- 2020
- Full Text
- View/download PDF
44. Prediction of T cell and B cell epitopes of the 22-, 47-, 56-, and 58-kDa proteins of Orientia tsutsugamushi
- Author
-
Li-Na Niu, Ting-Ting Fu, Man-Ling Chen, Yu-Ying Dong, Jin-Chun Tu, Zi-Hao Wang, Si-Qi Wang, Xuan Zhao, Nai-Xu Hou, Qian Chen, and Qiang Wu
- Subjects
orientia tsutsugamushi ,b cell epitopes ,t cell epitopes ,bioinformatic prediction ,Arctic medicine. Tropical medicine ,RC955-962 ,Biology (General) ,QH301-705.5 - Abstract
Objective: To predict B cell and T cell epitopes of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins. Methods: The sequences of 22-kDa, 47-kDa, 56-kDa and 58-kDa proteins which were derived from Orientia tsutsugamushi were analyzed by SOPMA, DNAstar, Bcepred, ABCpred, NetMHC, NetMHC II and IEDB. The 58-kDa tertiary structure model was built by MODELLER9.17. Results: The 22-kDa B-cell epitopes were located at positions 194-200, 20-26 and 143-154, whereas the T-cell epitopes were located at positions 154-174, 95-107, 17-25 and 57-65. The 47-kDa protein B-cell epitopes were at positions 413-434, 150-161 and 283-322, whereas the T-cell epitopes were located at positions 129-147, 259-267, 412-420 and 80-88. The 56-kDa protein B-cell epitopes were at positions 167-173, 410-419 and 101-108, whereas the T-cell epitopes were located at positions 88-104, 429-439, 232-240 and 194-202. The 58-kDa protein B-cell epitopes were at positions 312-317, 540-548 and 35-55, whereas the T-cell epitopes were located at positions 415-434, 66-84 and 214-230. Conclusions: We identified candidate epitopes of 22-kDa, 47-kDa, 56-kDa and 58- kDa proteins from Orientia tsutsugamushi. In the case of 58-kDa, the dominant antigen is displayed on tertiary structure by homology modeling. Our findings will help target additional recombinant antigens with strong specificity, high sensitivity, and stable expression and will aid in their isolation and purification. more...
- Published
- 2019
- Full Text
- View/download PDF
45. In silico prediction of the epitopes for the immunogenic proteins present in Mycobacterium avium subsp. paratuberculosis
- Author
-
D SWATHI, S SARANYA, A RAJA, K VIJAYARANI, and K KUMANAN
- Subjects
Immunogenic proteins ,3D modeling ,Mycobaterium avium ,T cell Epitopes ,ZDock ,Animal culture ,SF1-1100 - Abstract
Johne’s disease caused by Mycobacterium avium subsp. paratuberculosis is a widespread problem in ruminants worldwide. Diagnosis of the disease during the early stages of infection is difficult. In search of newer proteins with antigenic and immunogenic characters, in silico epitope analysis of the immunogenic proteins was performed which identifies the proteins expressed during the early stages of infection and which could stimulate cell mediated immune response. T cell epitopes were predicted for the six immunogenic proteins and the epitopes were sorted based on the percentile ranking and repetition among MHC Class I alleles. 3D modeling and protein-protein interaction studies revealed that ELPLPQTYVD, DVVGYDRTQD, PDLQSVLGATPGAG, DGLRAQDD, DGLRAQDD and PGHVTDD epitopes interact with the MHC Class I molecule through hydrogen bonding. These epitopes are identified as potent candidates for the immunodiagnostic studies and could be further evaluated using in vitro studies. more...
- Published
- 2020
- Full Text
- View/download PDF
46. Low HLA binding of diabetes-associated CD8+ T-cell epitopes is increased by post translational modifications
- Author
-
John Sidney, Jose Luis Vela, Dave Friedrich, Ravi Kolla, Matthias von Herrath, Johnna D. Wesley, and Alessandro Sette
- Subjects
Diabetes ,Insulin ,T cell epitopes ,Class I MHC ,HLA-peptide binding affinity ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background Type 1 diabetes (T1D) is thought to be an autoimmune disease driven by anti-islet antigen responses and mediated by T-cells. Recent published data suggests that T-cell reactivity to modified peptides, effectively neoantigens, may promote T1D. These findings have given more credence to the concept that T1D may not be solely an error of immune recognition but may be propagated by errors in protein processing or in modifications to endogenous peptides occurring as result of hyperglycemia, endoplasmic reticulum (ER) stress, or general beta cell dysfunction. In the current study, we hypothesized that diabetes-associated epitopes bound human leukocyte antigen (HLA) class I poorly and that post-translational modifications (PTM) to key sequences within the insulin-B chain enhanced peptide binding to HLA class I, conferring the CD8+ T-cell reactivity associated with T1D. Results We first identified, through the Immune Epitope Database (IEDB; www.iedb.org), 138 published HLA class I-restricted diabetes-associated epitopes reported to elicit positive T-cell responses in humans. The peptide binding affinity for their respective restricting allele(s) was evaluated in vitro. Overall, 75% of the epitopes bound with a half maximal inhibitory concentration (IC50) of 8250 nM or better, establishing a reference affinity threshold for HLA class I-restricted diabetes epitopes. These studies demonstrated that epitopes from diabetes-associated antigens bound HLA with a lower affinity than those of microbial origin (binding threshold of 500 nM for 85% of the epitopes). Further predictions suggested that diabetes epitopes also bind HLA class I with lower affinity than epitopes associated with other autoimmune diseases. Therefore, we measured the effect of common PTM (citrullination, chlorination, deamidation, and oxidation) on HLA-A*02:01 binding of insulin-B-derived peptides, compared to native peptides. We found that these modifications increased binding for 44% of the insulin-B epitopes, but only 15% of the control peptides. Conclusions These results demonstrate that insulin-derived epitopes, commonly associated with T1D, generally bind HLA class I poorly, but can be subject to PTM that improve their binding capacity and may, in part, be responsible for T-cell activation in T1D and subsequent beta cell death. more...
- Published
- 2018
- Full Text
- View/download PDF
47. Prediction and Identification of Epitopes in the Emy162 Antigen of Echinococcus multilocularis.
- Author
-
Pang, Ming-Quan, Tang, Feng, Wang, Hai-Jiu, Zhou, Ying, Ren, Li, Li, Run-Le, Zhou, Hu, Wan, Chen-Fei, Liu, Chuan-Chuan, Yangdan, Cai-Rang, and Fan, Hai-Ning
- Subjects
ECHINOCOCCUS multilocularis ,EPITOPES ,ANTIGENS ,T cells ,FORECASTING ,BIOINFORMATICS software ,PARASITISM - Abstract
Introduction: Alveolar echinococcosis (AE) is a zoonotic disease caused by the parasitism of Echinococcus multilocularis larvae in the intermediate host or the final host. This study aims to identify and analyze the B-cell and T-cell (Th1, Th2 and Th17) epitopes of E. multilocularis antigen Emy162. Methods: (1) The secondary structural characteristics of the Emy162 protein were predicted by bioinformatics software to further predict the potential T- and B-cell epitopes. (2) The dominant antigen epitopes were detected by ELISA through the reaction of patient serum with small B-cell antigen peptide and assessing the proliferation of splenic lymphocytes of mice immunized with Emy162. (3) The expression of cytokines in splenic lymphocytes of mice stimulated by small T-cell antigen peptides was detected by ELISA, ELISpot and flow cytometry to enable the identification of the T-cell epitopes. Results: (1) The high-scored T-cell epitopes were located at positions E7-13, E36-41, E80-89, E87-96, E97-106 and E129-139, while B-cell epitopes were located at positions E7-13, E19-27, E28-36, E37-48, E78-83, E101-109, E112-121 and E129-139. (2) The three advanced antigen epitopes of Emy162 were E19-27, E112-121 and E129-139. (3) The four Th1 advanced antigen epitopes of Emy162 were E7-13, E36-41, E80-89 and E129-139. The three Th2 advanced antigen epitopes were E36-41, E87-96 and E97-106. The three Th17 advanced antigen epitopes were E36-41, E87-96 and E97-106. Conclusion: (1) The Emy162 protein has advanced antigenicity and numerous potential epitopes. Six T-cell and eight B-cell dominant epitopes were revealed using bioinformatics methods. (2) There are three dominant B-cell epitopes, four dominant Th1 epitopes, three dominant Th2 epitopes, and three dominant Th17 epitopes in the Emy162 antigen. [ABSTRACT FROM AUTHOR] more...
- Published
- 2020
- Full Text
- View/download PDF
48. Immunogenicity of Immunotoxins Containing Pseudomonas Exotoxin A: Causes, Consequences, and Mitigation.
- Author
-
Mazor, Ronit and Pastan, Ira
- Subjects
ANTIBODY-toxin conjugates ,B cell receptors ,EXOTOXIN ,PHARMACOLOGY ,DRUG accessibility - Abstract
Immunotoxins are cytolytic fusion proteins developed for cancer therapy, composed of an antibody fragment that binds to a cancer cell and a protein toxin fragment that kills the cell. Pseudomonas exotoxin A (PE) is a potent toxin that is used for the killing moiety in many immunotoxins. Moxetumomab Pasudotox (Lumoxiti) contains an anti-CD22 Fv and a 38 kDa portion of PE. Lumoxiti was discovered in the Laboratory of Molecular Biology at the U.S. National Cancer Institute and co-developed with Medimmune/AstraZeneca to treat hairy cell leukemia. In 2018 Lumoxiti was approved by the US Food and Drug Administration for the treatment of drug-resistant Hairy Cell Leukemia. Due to the bacterial origin of the killing moiety, immunotoxins containing PE are highly immunogenic in patients with normal immune systems, but less immunogenic in patients with hematologic malignancies, whose immune systems are often compromised. LMB-100 is a de-immunized variant of the toxin with a humanized antibody that targets mesothelin and a PE toxin that was rationally designed for diminished reactivity with antibodies and B cell receptors. It is now being evaluated in clinical trials for the treatment of mesothelioma and pancreatic cancer and is showing somewhat diminished immunogenicity compared to its un modified parental counterpart. Here we review the immunogenicity of the original and de-immunized PE immunotoxins in mice and patients, the development of anti-drug antibodies (ADAs), their impact on drug availability and their effect on clinical efficacy. Efforts to mitigate the immunogenicity of immunotoxins and its impact on immunogenicity will be described including rational design to identify, remove, or suppress B cell or T cell epitopes, and combination of immunotoxins with immune modulating drugs. [ABSTRACT FROM AUTHOR] more...
- Published
- 2020
- Full Text
- View/download PDF
49. Experimental analysis of T cell epitopes for designing liver cancer vaccine predicted by system-level immunoinformatics approach.
- Author
-
Muhammad, Syed Aun, Zafar, Sidra, Rizvi, Samana Zahra, Imran, Imran, Munir, Fahad, Jamshed, Muhammad Babar, Ali, Amjad, Xiaogang Wu, Shahid, Numan, Zaeem, Muhammad, and Qiyu Zhang
- Abstract
Liver cancer is a worldwide disease, and, currently, due to the poor prognostic and therapeutic options of liver cancer, we investigated the T cell epitopes as potential therapeutic vaccine candidates to get the benefit of experimental processes and utilize the complete ability of the immune system compared with other artificial ex vivo proliferation of T cells. Activation of T cells targets and kills several tumors, developing a strong rationale for the improvement of immunotherapeutic strategies to cancer therapy. To predict T cell epitopes for liver cancer, we designed a comprehensive immunoinformatics framework involving data mining, immunogenicity prediction, functional proteomic analysis, conservation studies, molecular modeling, and in vivo validation analysis. We found the binding affinity of antigenic peptides with major histocompatibility complex (MHC) I molecules to control the cancerous activity. Five extracellular antigenic proteins, including complement protein (C6), serotransferrin, coagulation factor XIII B, serum albumin (ALB), and prothrombin, were identified. We predicted and synthesized T cell epitopes to human leukocytes antigen-A*01:01 allele of MHC class I molecule. The hematological assay and IgG ELISA showed that C6 and ALB epitopes induced the production of lymphocytes, granulocytes, and peptide-specific IgG in immunized rats. We observed substantial high levels of granzymes B in serum samples of C6 and ALB compared with control, indicating the activity of cytotoxic T cells. We concluded that C6 and ALB are likely to contain potential epitopes for the induction of protective effector molecules, supporting the feasibility of therapeutic peptide-based vaccine for liver cancer. NEW & NOTEWORTHY We observed substantial high levels of granzymes B in serum samples of component C6 (C6) and albumin (ALB) compared with control, indicating the activity of cytotoxic T cells. We concluded that C6 and ALB are likely to contain potential epitopes for the induction of protective effector molecules, supporting the feasibility of therapeutic peptide-based vaccine for liver cancer. [ABSTRACT FROM AUTHOR] more...
- Published
- 2020
- Full Text
- View/download PDF
50. SARS-CoV-2 T Cell Responses Elicited by COVID-19 Vaccines or Infection Are Expected to Remain Robust against Omicron
- Author
-
Syed Faraz Ahmed, Ahmed Abdul Quadeer, and Matthew R. McKay
- Subjects
SARS-CoV-2 ,COVID-19 ,Omicron ,variants ,T cell epitopes ,mutations ,Microbiology ,QR1-502 - Abstract
Omicron, the most recent SARS-CoV-2 variant of concern (VOC), harbours multiple mutations in the spike protein that were not observed in previous VOCs. Initial studies suggest Omicron to substantially reduce the neutralizing capability of antibodies induced from vaccines and previous infection. However, its effect on T cell responses remains to be determined. Here, we assess the effect of Omicron mutations on known T cell epitopes and report data suggesting T cell responses to remain broadly robust against this new variant. more...
- Published
- 2022
- Full Text
- View/download PDF
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.