T-cell Epitope-based Vaccine Design for Nipah Virus by Reverse Vaccinology Approach

2020 ◽  
Vol 23 (8) ◽  
pp. 788-796
Author(s):  
Praveen K.P. Krishnamoorthy ◽  
Sekar Subasree ◽  
Udhayachandran Arthi ◽  
Mohammad Mobashir ◽  
Chirag Gowda ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Vaccine Development ◽  
Nipah Virus ◽  
3D Structure ◽  
Cell Epitope ◽  
Class Ii ◽  
Class I ◽  
Reverse Vaccinology ◽  
Stable Complex

Aim and Objective: Nipah virus (NiV) is a zoonotic virus of the paramyxovirus family that sporadically breaks out from livestock and spreads in humans through breathing resulting in an indication of encephalitis syndrome. In the current study, T cell epitopes with the NiV W protein antigens were predicted. Materials and Methods: Modelling of unavailable 3D structure of W protein followed by docking studies of respective Human MHC - class I and MHC - class II alleles predicted was carried out for the highest binding rates. In the computational analysis, epitopes were assessed for immunogenicity, conservation, and toxicity analysis. T – cell-based vaccine development against NiV was screened for eight epitopes of Indian - Asian origin. Results: Two epitopes, SPVIAEHYY and LVNDGLNII, have been screened and selected for further docking study based on toxicity and conservancy analyses. These epitopes showed a significant score of -1.19 kcal/mol and 0.15 kcal/mol with HLA- B*35:03 and HLA- DRB1 * 07:03, respectively by using allele - Class I and Class II from AutoDock. These two peptides predicted by the reverse vaccinology approach are likely to induce immune response mediated by T – cells. Conclusion: Simulation using GROMACS has revealed that LVNDGLNII epitope forms a more stable complex with HLA molecule and will be useful in developing the epitope-based Nipah virus vaccine.

scholarly journals Prediction of Epitope-Based Peptides for the Utility of Vaccine Development from Fusion and Glycoprotein of Nipah Virus Using In Silico Approach

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
M. Sadman Sakib ◽  
Md. Rezaul Islam ◽  
A. K. M. Mahbub Hasan ◽  
A. H. M. Nurun Nabi
Keyword(s):  
B Cell ◽  
In Silico ◽  
Vaccine Development ◽  
Nipah Virus ◽  
Cell Epitope ◽  
Class Ii ◽  
Host Cells ◽  
Class I ◽  
Cell Mediated Immunity ◽  
Population Coverage

This study aims to design epitope-based peptides for the utility of vaccine development by targeting glycoprotein G and envelope protein F of Nipah virus (NiV) that, respectively, facilitate attachment and fusion of NiV with host cells. Using various databases and tools, immune parameters of conserved sequence(s) from G and F proteins of different isolates of NiV were tested to predict probable epitope(s). Binding analyses of the peptides with MHC class-I and class-II molecules, epitope conservancy, population coverage, and linear B cell epitope prediction were analyzed. Predicted peptides interacted with seven or more MHC alleles and illustrated population coverage of more than 99% and 95%, for G and F proteins, respectively. The predicted class-I nonamers, SLIDTSSTI and EWISIVPNF, superimposed on the putative decameric B cell epitopes, were also identified as core sequences of the most probable class-II 15-mer peptides GPKVSLIDTSSTITI and EWISIVPNFILVRNT. These peptides were further validated for their binding to specific HLA alleles using in silico docking technique. Our in silico analysis suggested that the predicted epitopes, either GPKVSLIDTSSTITI or EWISIVPNFILVRNT, could be a better choice as universal vaccine component against NiV irrespective of different isolates which may elicit both humoral and cell-mediated immunity.

scholarly journals Identification of MHC class II restricted T-cell-mediated reactivity against MHC class I binding Mycobacterium tuberculosis peptides

Immunology ◽  
2011 ◽  
Vol 132 (4) ◽  
pp. 482-491 ◽  
Author(s):  
Mingjun Wang ◽  
Sheila T. Tang ◽  
Anette Stryhn ◽  
Sune Justesen ◽  
Mette V. Larsen ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I

Mouse Schwann cells activate MHC class I and II restricted T-cell responses, but require external peptide processing for MHC class II presentation

2010 ◽  
Vol 37 (2) ◽  
pp. 483-490 ◽  
Author(s):  
Gerd Meyer zu Hörste ◽  
Holger Heidenreich ◽  
Anne K. Mausberg ◽  
Helmar C. Lehmann ◽  
Anneloor L.M.A. ten Asbroek ◽  
...  
Keyword(s):  
T Cell ◽  
Schwann Cells ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
T Cell Responses ◽  
Class Ii ◽  
Class I ◽  
Peptide Processing ◽  
Cell Responses

scholarly journals A Class II-Restricted CD8γ13 T-Cell Clone Protects During Chlamydia muridarum Genital Tract Infection

2020 ◽  
Vol 221 (11) ◽  
pp. 1895-1906
Author(s):  
Raymond M Johnson ◽  
Norma Olivares-Strank ◽  
Gang Peng
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cd8 T Cells ◽  
Genital Tract ◽  
Cell Clone ◽  
Class Ii ◽  
Class I ◽  
T Cell Clone ◽  
Tract Infections

Abstract Background The T-cell response to chlamydia genital tract infections in humans and mice is unusual because the majority of antigen-specific CD8 T cells are not class I restricted (referred to here as “unrestricted” or “atypical”). We previously reported that a subset of unrestricted murine chlamydia-specific CD8 T cells had a cytokine polarization pattern that included interferon (IFN)-γ and interleukin (IL)-13. Methods In this study, we investigated the transcriptome of CD8γ13 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD8γ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD8γ13 T-cell clone to determine whether either influenced bacterial clearance or immunopathology during Chlamydia muridarum genital tract infections. Results To our surprise, an adoptively transferred CD8γ13 T-cell clone was remarkably proficient at preventing chlamydia immunopathology, whereas the multifunctional Tc1 clone did not enhance clearance or significantly alter immunopathology. Mapping studies with major histocompatibility complex (MHC) class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T-cell clones are MHC class II restricted. Conclusions The MHC class II-restricted CD8 T cells may play an important role in protection from intracellular pathogens that limit class I antigen presentation or diminish CD4 T-cell numbers or impair their function.

scholarly journals Peptide HER2(776–788) represents a naturally processed broad MHC class II-restricted T cell epitope

2001 ◽  
Vol 85 (10) ◽  
pp. 1527-1534 ◽  
Author(s):  
R Sotiriadou ◽  
S A Perez ◽  
A D Gritzapis ◽  
P A Sotiropoulou ◽  
H Echner ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Cell Epitope ◽  
Class Ii ◽  
T Cell Epitope

Human T Cells with Distinct Specificities Mediate Graft-Versus-Leukemia Reactivity and Xenogeneic Graft-Versus-Host Disease in a NOD/Scid Mouse Model for Human Acute Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1330-1330
Author(s):  
Sanja Stevanovic ◽  
Bart Nijmeijer ◽  
Marianke LJ Van Schie ◽  
Roelof Willemze ◽  
Marieke Griffioen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Class I ◽  
T Cell Clones ◽  
Cell Clones ◽  
Human T Cells

Abstract Abstract 1330 Poster Board I-352 Immunodeficient mice inoculated with human leukemia can be used as a model to investigate Graft-versus-Leukemia (GvL) effects of donor lymphocyte infusions (DLIs). In addition to GvL reactivity, treatment with DLI induces xenogeneic Graft-versus-Host Disease (GvHD) in mice, characterized by pancytopenia and weight loss. In patients treated with DLI for relapsed or residual leukemia after allogeneic stem cell transplantation, immune responses against non-leukemic cells may also cause GvHD. It has been suggested that GvL reactivity and GvHD, which co-develop in vivo, can be separated and that distinct T cells exist with the specific capacity to mediate GvL reactivity or GvHD. Since adoptive T cell transfer models that allow analysis of separation of GvL and GvHD are rare, we aimed to establish whether GvL reactivity and xenogeneic GvHD could be separated using our model of human leukemia-engrafted NOD/scid mouse after treatment with human donor T cells. In this study, non-conditioned NOD/scid mice engrafted with primary human acute lymphoblastic leukemic cells were treated with CD3+ DLI. Established tumors were effectively eliminated by emerging human T cells, but also induced xenogeneic GvHD. Flowcytometric analysis demonstrated that the majority of emerging CD8+ and CD4+ T cells were activated (HLA-DR+) and expressed an effector memory phenotype (CD45RA-CD45RO+CCR7-). To investigate whether GvL reactivity and xenogeneic GvHD were mediated by the same T cells showing reactivity against both human leukemic and murine cells, or displaying distinct reactivity against human leukemic and murine cells, we clonally isolated and characterized the T cells during the GvL response and xenogeneic GvHD. T cell clones were analyzed for reactivity against primary human leukemic cells and primary NOD/scid hematopoietic (BM and spleen cells) and non-hematopoietic (skin fibroblasts) cells in IFN-g ELISA. Isolated CD8+ and CD4+ T cell clones were shown to recognize either human leukemic or murine cells, indicating that GvL response and xenogeneic GvHD were mediated by different human T cells. Flowcytometric analysis demonstrated that all BM and spleen cells expressed MHC class I, whereas only 1-3 % of the cells were MHC class II +. Primary skin fibroblasts displayed low MHC class I and completely lacked MHC class II expression. Xeno-reactive CD8+ T cell clones were shown to recognize all MHC class I + target cells and xeno-reactive CD4+ T cells clones displayed reactivity only against MHC class II + target cells. To determine the MHC restriction of xeno-reactive T cell clones, NOD/scid bone marrow (BM) derived dendritic cells (DC) expressing high levels of murine MHC class I and class II were tested for T cell recognition in the presence or absence of murine MHC class I and class II monoclonal antibodies in IFN-g ELISA. Xeno-reactive CD8+ T cell clones were shown to be MHC class I (H-2Kd or H-2Db) restricted, whereas xeno-reactive CD4+ T cell clones were MHC class II (I-Ag7) restricted, indicating that xeno-reactivity reflects genuine human T cell response directed against allo-antigens present on murine cells. Despite production of high levels of IFN-gamma, xeno-reactive CD8+ and CD4+ T cell clones failed to exert cytolytic activity against murine DC, as determined in a 51Cr-release cytotoxicity assay. Absence of cytolysis by CD8+ T cell clones, which are generally considered as potent effector cells, may be explained by low avidity interaction between human T cells and murine DC, since flowcytometric analysis revealed sub-optimal activation of T cells as measured by CD137 expression and T cell receptor downregulation upon co-culture with murine DC, and therefore these results indicate that xenogeneic GvHD in this model is likely to be mediated by cytokines. In conclusion, in leukemia-engrafted NOD/scid mice treated with CD3+ DLI, we show that GvL reactivity and xenogeneic GvHD are mediated by separate human T cells with distinct specificities. All xeno-reactive T cell clones showed genuine recognition of MHC class I or class II associated allo-antigens on murine cells similar as GvHD-inducing human T cells. These data suggest that our NOD/scid mouse model of human acute leukemia may be valuable for studying the effectiveness and specificity of selectively enriched or depleted T cells for adoptive immunotherapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Genetic Dissection of Primary and Secondary Responses to a Widespread Natural Pathogen of the Gut,Eimeria vermiformis

2000 ◽  
Vol 68 (11) ◽  
pp. 6273-6280 ◽  
Author(s):  
Adrian L. Smith ◽  
Adrian C. Hayday
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Primary Response ◽  
Class I ◽  
Class Ii Mhc ◽  
Ifn Γ ◽  
Αβ T Cells

ABSTRACT Because most pathogens initially challenge the body at epithelial surfaces, it is important to dissect the mechanisms that underlie T-cell responses to infected epithelial cells in vivo. The coccidian parasites of the genus Eimeria are protozoan gut pathogens that elicit a potent, protective immune response in a wide range of host species. CD4+ αβ T cells and gamma interferon (IFN-γ) are centrally implicated in the primary immunoprotective response. To define any additional requirements for the primary response and to develop a comparison between the primary and the secondary response, we have studied Eimeria infections of a broad range of genetically altered mice. We find that a full-strength primary response depends on β2-microglobulin (class I major histocompatibility complex [MHC] and class II MHC and on IFN-γ and interleukin-6 (IL-6) but not on TAP1, perforin, IL-4, Fas ligand, or inducible nitric oxide synthetase. Indeed, MHC class II-deficient and IFN-γ-deficient mice are as susceptible to primary infection as mice deficient in all αβ T cells. Strikingly, the requirements for a highly effective αβ-T-cell-driven memory response are less stringent, requiring neither IFN-γ nor IL-6 nor class I MHC. The class II MHC dependence was also reduced, with adoptively transferable immunity developing in MHC class II−/− mice. Besides the improved depiction of an immune response to a natural gut pathogen, the finding that effective memory can be elicited in the absence of primary effector responses appears to create latitude in the design of vaccine strategies.

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

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

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

scholarly journals Potential immune epitope map for structural proteins of SARS-CoV-2

2020 ◽  
Author(s):  
Yengkhom Damayanti Devi ◽  
Himanshu Ballav Goswami ◽  
Sushmita Konwar ◽  
Chandrima Doley ◽  
Anutee Dolley ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Cell Epitope ◽  
Class I ◽  
Structural Proteins ◽  
S Protein ◽  
N Protein ◽  
B Cell Epitope

Abstract Researchers around the world are developing more than 145 vaccines (DNA/mRNA/whole-virus/viral-vector/protein-based/repurposed vaccine) against the SARS-CoV-2 and 21 vaccines are in human trials. However, a limited information is available about which SARS-CoV-2 proteins are recognized by human B- and T-cell immune responses. Using a comprehensive computational prediction algorithm and stringent selection criteria, we have predicted and identified potent B- and T-cell epitopes in the structural proteins of SARS-CoV and SARS-CoV-2. The amino acid residues spanning the predicted linear B-cell epitope in the RBD of S protein (370-NSASFSTFKCYGVSPTKLNDLCFTNV-395) have recently been identified for interaction with the CR3022, a previously described neutralizing antibody known to neutralize SARS-CoV-2 through binding to the RBD of the S protein. Intriguingly, most of the amino acid residues spanning the predicted B-cell epitope (aa 331-NITNLCPFGEVFNATRFASVYAWNRK-356, 403-RGDEVRQIAPGQTGKIADYNYKLPD-427 and aa 437- NSNNLDSKVGGNYNYLYRLFRKSNL-461) of the S protein have been experimentally verified to interact with the cross-neutralizing mAbs (S309 and CB6) in an ACE2 receptor-S protein interaction independent-manner. In addition, we found that computationally predicted epitope of S protein (370-395) is likely to function as both linear B-cell and MHC class II epitope. Similarly, 403-27 and 437-461 peptides of S protein were predicted as linear B cell and MHC class I epitope while, 177-196 and 1253-1273 peptides of S protein were predicted as linear and conformational B cell epitope. We found MHC class I epitope 316-GMSRIGMEV-324 predicted as high affinity epitope (HLA-A*02:03, HLA-A*02:01, HLA-A*02:06) common to N protein of both SARS-CoV-2 and SARS-CoV (N317-325) was previously shown to induce interferon-gamma (IFN-γ) in PBMCs of SARS-recovered patients. Interestingly, two MHC class I epitopes, 1041-GVVFLHVTY-1049 (HLA-A*11:01, HLA-A*68:01, HLA-A*03:01) and 1202-FIAGLIAIV-1210 (HLA-A*02:06, HLA-A*68:02) derived from SARS-CoV S protein with epitope conservancy between 85 to 100% with S protein of SARS-CoV-2 was experimentally verified using PBMCs derived from SARS-CoV patients. We observed that HLA-A*02:01, HLA-A*02:03, HLA-A*02:06, HLA-A*11:01, HLA-A*30:01, HLA-A*68:01, HLA-A*68:02, HLA-B*15:01 and HLA-B*35:01 have been predicted to bind to the maximum number of MHC class I epitope (based on the criterion of allele predicted to bind more than 30 epitopes) of S protein of SARS-CoV-2. Similarly, we observed that HLA-A*02:06, HLA-A*30:01, HLA-A*30:02, HLA-A*31:01, HLA-A*32:01, HLA-A*68:01, HLA-A*68:02, HLA-B*15:01 and HLA-B*35:01 are predicted to bind to the maximum number of MHC class I epitope of N protein of SARS-CoV-2. We found that HLA-DRB1*04:01, HLA-DRB1*04:05, HLA-DRB1*13:02, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01, HLA-DRB5*01:01, HLA-DQA1*04:01, DQB1*04:02, HLA-DPA1*02:01, DPB1*01:01, HLA-DPA1*01:03, DPB1*02:01, HLA-DPA1*01:03, DPB1*04:01, HLA-DPA1*03:01, DPB1*04:02, HLA-DPA1*02:01, DPB1*05:01, HLA-DPA1*02:01, and DPB1*14:01 are predicted to bind to the maximum number of MHC class II epitope of S protein of SARS-CoV-2. Alleles such as HLA-DRB1*04:01, HLA-DRB1*07:01, HLA-DRB1*08:02, HLA-DRB1*09:01, HLA-DRB1*11:01, HLA-DRB1*13:02, HLA-DRB3*02:02, HLA-DRB5*01:01, HLA-DQA1*01:02, DQB1*06:02, DPB1*05:01 and HLA-DPA1*02:01 are found to interact with the maximum number of MHC class II epitope of N protein of SARS-CoV-2. Using the IEDB tool we found the occurrence of HLA alleles with population coverage of around 99% throughout the world. The findings of computational predictions of mega-pool of B- and T-cell epitopes identified in the four main structural proteins of SARS-CoV-2 provides a platform for future experimental validations and the results of present works support the use of RBD or the full-length S and N proteins in an effort towards designing of recombinant protein-based vaccine and a serological diagnostic assay for SARS-CoV-2.

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