scholarly journals Immunoinformatics Analysis of SARS-CoV-2 ORF1ab Polyproteins to Identify Promiscuous and Highly Conserved T-Cell Epitopes to Formulate Vaccine for Indonesia and the World Population

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1459
Author(s):  
Marsia Gustiananda ◽  
Bobby Prabowo Sulistyo ◽  
David Agustriawan ◽  
Sita Andarini
Keyword(s):  
T Cell ◽  
Cell Epitope ◽  
Docking Simulation ◽  
Human Leukocyte ◽  
In Vitro Study ◽  
Hla Class I ◽  
World Population ◽  
T Cell Epitopes ◽  
Docking Simulations

SARS-CoV-2 and its variants caused the COVID-19 pandemic. Vaccines that target conserved regions of SARS-CoV-2 and stimulate protective T-cell responses are important for reducing symptoms and limiting the infection. Seven cytotoxic (CTL) and five helper T-cells (HTL) epitopes from ORF1ab were identified using NetCTLpan and NetMHCIIpan algorithms, respectively. These epitopes were generated from ORF1ab regions that are evolutionary stable as reflected by zero Shannon’s entropy and are presented by 56 human leukocyte antigen (HLA) Class I and 22 HLA Class II, ensuring good coverage for the Indonesian and world population. Having fulfilled other criteria such as immunogenicity, IFNγ inducing ability, and non-homology to human and microbiome peptides, the epitopes were assembled into a vaccine construct (VC) together with β-defensin as adjuvant and appropriate linkers. The VC was shown to have good physicochemical characteristics and capability of inducing CTL as well as HTL responses, which stem from the engagement of the vaccine with toll-like receptor 4 (TLR4) as revealed by docking simulations. The most promiscuous peptide 899WSMATYYLF907 was shown via docking simulation to interact well with HLA-A*24:07, the most predominant allele in Indonesia. The data presented here will contribute to the in vitro study of T-cell epitope mapping and vaccine design in Indonesia.

scholarly journals Identification of an immunogenic CD8+ T-cell epitope derived from γ-globin, a putative tumor-associated antigen for juvenile myelomonocytic leukemia

Blood ◽  
2006 ◽  
Vol 108 (8) ◽  
pp. 2662-2668 ◽  
Author(s):  
Naoto Hirano ◽  
Marcus O. Butler ◽  
Zhinan Xia ◽  
Alla Berezovskaya ◽  
Andrew P. Murray ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Epitope ◽  
Human Leukocyte ◽  
Cd8 T Cell ◽  
Juvenile Myelomonocytic Leukemia ◽  
Clinical Activity ◽  
T Cell Epitopes ◽  
Intact Cells ◽  
Myelomonocytic Leukemia

AbstractJuvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative disorder. Although allogeneic stem cell transplantation can induce long-term remissions, relapse rates remain high and innovative approaches are needed. Since donor lymphocyte infusions have clinical activity in JMML, T-cell-mediated immunotherapy could provide a nonredundant treatment approach to compliment current therapies. γ-Globin, an oncofetal protein overexpressed by clonogenic JMML cells, may serve as a target of an antitumor immune response. We predicted 5 γ-globin-derived peptides as potential human leukocyte antigen (HLA)-A2 restricted cytotoxic T lymphocyte (CTL) epitopes and showed that 4 (g031, g071, g105, and g106) bind A2 molecules in vitro. Using an artificial antigen-presenting cell (aAPC) that can process both the N- and C-termini of endogenously expressed proteins, we biochemically confirmed that g105 is naturally processed and presented by cell surface A2. Furthermore, g105-specific CD8+ CTLs generated from A2-positive healthy donors were able to specifically cytolyze γ-globin+, but not γ-globin- JMML cells in an A2-restricted manner. These results suggest that this aAPC-based approach enables the biochemical identification of CD8+ T-cell epitopes that are processed and presented by intact cells, and that CTL immunotherapy of JMML could be directed against the γ-globin-derived epitope g105.

scholarly journals West Nile Virus Vaccine Design by T Cell Epitope Selection: In Silico Analysis of Conservation, Functional Cross-Reactivity with the Human Genome, and Population Coverage

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Frances M. Waller ◽  
Pedro A. Reche ◽  
Darren R. Flower
Keyword(s):  
West Nile Virus ◽  
T Cell ◽  
Cell Epitope ◽  
Human Leukocyte ◽  
Medical Intervention ◽  
Cross Reactivity ◽  
World Population ◽  
T Cell Epitopes ◽  
West Nile ◽  
Multiple Sequence

West Nile Virus (WNV) causes a debilitating and life-threatening neurological disease in humans. Since its emergence in Africa 50 years ago, new strains of WNV and an expanding geographical distribution have increased public health concerns. There are no licensed therapeutics against WNV, limiting effective infection control. Vaccines represent the most efficacious and efficient medical intervention known. Epitope-based vaccines against WNV remain significantly underexploited. Here, we use a selection protocol to identify a set of conserved prevalidated immunogenic T cell epitopes comprising a putative WNV vaccine. Experimentally validated immunogenic WNV epitopes and WNV sequences were retrieved from the IEDB and West Nile Virus Variation Database. Clustering and multiple sequence alignment identified a smaller subset of representative sequences. Protein variability analysis identified evolutionarily conserved sequences, which were used to select a diverse set of immunogenic candidate T cell epitopes. Cross-reactivity and human leukocyte antigen-binding affinities were assessed to eliminate unsuitable epitope candidates. Population protection coverage (PPC) quantified individual epitopes and epitope combinations against the world population. 3 CD8+ T cell epitopes (ITYTDVLRY, TLARGFPFV, and SYHDRRWCF) and 1 CD4+ epitope (VTVNPFVSVATANAKVLI) were selected as a putative WNV vaccine, with an estimated PPC of 97.14%.

scholarly journals Construction and Evaluation of a Novel Recombinant T Cell Epitope-Based Vaccine against Coccidioidomycosis

2012 ◽  
Vol 80 (11) ◽  
pp. 3960-3974 ◽  
Author(s):  
Brady J. Hurtgen ◽  
Chiung-Yu Hung ◽  
Gary R. Ostroff ◽  
Stuart M. Levitz ◽  
Garry T. Cole
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cell Epitope ◽  
T Cell Epitopes ◽  
Protein Vaccine ◽  
T Helper 1 ◽  
Human Major Histocompatibility Complex ◽  
Content Type ◽  
Mhc Ii

ABSTRACTClinical and animal studies of coccidioidomycosis have demonstrated that activated CD4+T lymphocytes are essential for protection against this fungal respiratory disease. We previously reported a vaccine againstCoccidioidesinfection which contained three recombinant CD4+T cell-reactive proteins and induced a robust, protective immune response in mice. Due to the anticipated high cost of production and clinical assessment of this multivalent vaccine, we generated a single protein which contained immunodominant T cell epitopes of the three polypeptides. Epitopes were initially identified by computational prediction of their ability to bind promiscuously to human major histocompatibility complex class II (MHC II) molecules. Cellular immunoassays confirmed the immunogenicity of the synthesized epitope peptides, whilein vitrobinding assays revealed a range of peptide affinity for MHC II. A DNA construct was synthesized for bacterial expression of a recombinant protein vaccine which contained five epitopes with the highest affinity for human MHC II, each fused with leader and spacer peptides proposed to optimize epitope processing and presentation to T cell receptors. Recall assays of immune T lymphocytes obtained from human MHC II-expressing HLA-DR4 transgenic mice confirmed that 4 of the 5 epitope peptides were processed. Mice immunized with the epitope-based vaccine admixed with a synthetic oligodeoxynucleotide adjuvant or loaded into yeast glucan particles and then challenged intranasally withCoccidioidesshowed early lung infiltration of activated T helper-1 (Th1), Th2, and Th17 cells, elevated gamma interferon (IFN-γ) and interleukin (IL)-17 production, significant reduction of fungal burden, and prolongation of survival compared to nonvaccinated mice. This is the first report of an epitope-based vaccine against coccidioidomycosis.

scholarly journals Immunoinformatics Approach Identified Two Highly Conserved B and T Cell Epitopes, LEASKRWAF and DSPLEASKRWAFRTG, for Effective Vaccine Design against Ebola and Marburg Viruses

2019 ◽  
pp. 1-16
Author(s):  
Md. Shahadat Hossain ◽  
Hasan Al. Reza ◽  
Mohammad Shahnoor Hossain
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Simulation Analysis ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Docking Simulation ◽  
Hemorrhagic Fever ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
Mhc Molecules

Aims: Ebola and Marburg viruses cause fatal hemorrhagic fever in both human and non-human primates. Absence of any licensed vaccine has further deteriorated the problem. In the present study, we aimed to design potential epitope based vaccines against these viruses using computational approaches. Methodology: By using various bioinformatics tools and databases, we analyzed the conserved glycoprotein sequences of Ebola and Marburg viruses and predicted two potential epitopes which may be used as peptide vaccines. Results: Using various B-cell and T-cell epitope prediction servers, four highly conserved epitopes were identified. Epitope conservancy analysis showed that  “LEASKRWAF” and “DSPLEASKRWAFRTG” epitopes were 100% and 93.62% conserved and the worldwide population coverage of “LEASKRWAF” interacting with MHC class I molecules and “DSPLEASKRWAFRTG” interacting with MHC class II molecules were 78.74% and 75.75% respectively. Immunoinformatics analysis showed that they are highly immunogenic, flexible and accessible to antibody. Molecular docking simulation analysis demonstrated a very significant interaction between epitopes and MHC molecules with lower binding energy. Cytotoxic analysis and ADMET test also supported their potential as vaccine candidates. Conclusion: In sum, our in silico approach demonstrated that both “LEASKRWAF” and “DSPLEASKRWAFRTG” hold the promise for the development of common vaccine against Ebola and Marburg viruses.

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

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

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

scholarly journals Designing multiepitope-based vaccine against Eimeria from immune mapped protein 1 (IMP-1) antigen using immunoinformatic approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thabile Madlala ◽  
Victoria T. Adeleke ◽  
Abiodun J. Fatoba ◽  
Moses Okpeku ◽  
Adebayo A. Adeniyi ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Docking Simulation ◽  
Cost Effective ◽  
Economic Loss ◽  
T Cell Epitopes ◽  
Live Vaccines ◽  
Physiochemical Parameters

AbstractDrug resistance against coccidiosis has posed a significant threat to chicken welfare and productivity worldwide, putting daunting pressure on the poultry industry to reduce the use of chemoprophylactic drugs and live vaccines in poultry to treat intestinal diseases. Chicken coccidiosis, caused by an apicomplexan parasite of Eimeria spp., is a significant challenge worldwide. Due to the experience of economic loss in production and prevention of the disease, development of cost-effective vaccines or drugs that can stimulate defence against multiple Eimeria species is imperative to control coccidiosis. This study explored Eimeria immune mapped protein-1 (IMP-1) to develop a multiepitope-based vaccine against coccidiosis by identifying antigenic T-cell and B-cell epitope candidates through immunoinformatic techniques. This resulted in the design of 7 CD8+, 21 CD4+ T-cell epitopes and 6 B-cell epitopes, connected using AAY, GPGPG and KK linkers to form a vaccine construct. A Cholera Toxin B (CTB) adjuvant was attached to the N-terminal of the multiepitope construct to improve the immunogenicity of the vaccine. The designed vaccine was assessed for immunogenicity (8.59968), allergenicity and physiochemical parameters, which revealed the construct molecular weight of 73.25 kDa, theoretical pI of 8.23 and instability index of 33.40. Molecular docking simulation of vaccine with TLR-5 with binding affinity of − 151.893 kcal/mol revealed good structural interaction and stability of protein structure of vaccine construct. The designed vaccine predicts the induction of immunity and boosted host's immune system through production of antibodies and cytokines, vital in hindering surface entry of parasites into host. This is a very important step in vaccine development though further experimental study is still required to validate these results.

scholarly journals A systematic, unbiased mapping of CD8+ and CD4+ T cell epitopes in Yellow Fever vaccinees

2020 ◽  
Author(s):  
Anette Stryhn ◽  
Michael Kongsgaard ◽  
Michael Rasmussen ◽  
Mikkel Nors Harndahl ◽  
Thomas Østerbye ◽  
...  
Keyword(s):  
T Cell ◽  
Yellow Fever ◽  
Cell Epitope ◽  
T Cell Responses ◽  
Hla Class I ◽  
Class I ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Cell Responses ◽  
Epitope Discovery

1.AbstractExamining CD8+ and CD4+ T cell responses after primary Yellow Fever vaccination in a cohort of 210 volunteers, we have identified and tetramer-validated 92 CD8+ and 50 CD4+ T cell epitopes, many inducing strong and prevalent (i.e. immunodominant) T cell responses. Restricted by 40 and 14 HLA-class I and II allotypes, respectively, these responses have wide population coverage and might be of considerable academic, diagnostic and therapeutic interest. The broad coverage of epitopes and HLA overcame the otherwise confounding effects of HLA diversity and non-HLA background providing the first evidence of T cell immunodomination in humans. Also, double-staining of CD4+ T cells with tetramers representing the same HLA-binding core, albeit with different flanking regions, demonstrated an extensive diversification of the specificities of many CD4+ T cell responses. We suggest that this could reduce the risk of pathogen escape, and that multi-tetramer staining is required to reveal the true magnitude and diversity of CD4+ T cell responses. Our T cell epitope discovery approach uses a combination of 1) overlapping peptides representing the entire Yellow Fever virus proteome to search for peptides containing CD4+ and/or CD8+ T cell epitopes, 2) predictors of peptide-HLA binding to suggest epitopes and their restricting HLA allotypes, 3) generation of peptide-HLA tetramers to identify T cell epitopes, and 4) analysis of ex vivo T cell responses to validate the same. This approach is systematic, exhaustive, and can be done in any individual of any HLA haplotype. It is all-inclusive in the sense that it includes all protein antigens and peptide epitopes, and encompasses both CD4+ and CD8+ T cell epitopes. It is efficient and, importantly, reduces the false discovery rate. The unbiased nature of the T cell epitope discovery approach presented here should support the refinement of future peptide-HLA class I and II predictors and tetramer technologies, which eventually should cover all HLA class I and II isotypes. We believe that future investigations of emerging pathogens (e.g. SARS-CoV-2) should include population-wide T cell epitope discovery using blood samples from patients, convalescents and/or long-term survivors, who might all hold important information on T cell epitopes and responses.

scholarly journals Immunogenicity of a Recombinant Influenza Virus Bearing Both the CD4+ and CD8+ T Cell Epitopes of Ovalbumin

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Bruno Garulli ◽  
Giuseppina Di Mario ◽  
Ester Sciaraffia ◽  
Yoshihiro Kawaoka ◽  
Maria R. Castrucci
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Cell Epitope ◽  
Cd8 T Cell ◽  
Influenza Viruses ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Additional Tool

Recombinant influenza viruses that bear the single immunodominant CD8+ T cell epitopeOVA257−264or the CD4+ T cell epitopeOVA323−339of the model antigen ovalbumin (OVA) have been useful tools in immunology. Here, we generated a recombinant influenza virus,WSN-OVAI/II, that bears both OVA-specific CD8+ and CD4+ epitopes on its hemagglutinin molecule. Live and heat-inactivatedWSN-OVAI/IIviruses were efficiently presented by dendritic cellsin vitroto OT-I TCR transgenic CD8+ T cells and OT-II TCR transgenic CD4+ T cells.In vivo,WSN-OVAI/IIvirus was attenuated in virulence, highly immunogenic, and protected mice from B16-OVA tumor challenge in a prophylactic model of vaccination. Thus,WSN-OVAI/IIvirus represents an additional tool, along with OVA TCR transgenic mice, for further studies on T cell responses and may be of value in vaccine design.

scholarly journals Computational Identification and Characterization of a Promiscuous T-Cell Epitope on the Extracellular Protein 85B ofMycobacteriumspp. for Peptide-Based Subunit Vaccine Design

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Md. Saddam Hossain ◽  
Abul Kalam Azad ◽  
Parveen Afroz Chowdhury ◽  
Mamoru Wakayama
Keyword(s):  
Molecular Docking ◽  
T Cell ◽  
Cell Epitope ◽  
Docking Simulation ◽  
Vaccine Design ◽  
Extracellular Protein ◽  
T Cell Epitope ◽  
T Cell Epitopes ◽  
Hla Alleles ◽  
Mhc Molecules

Tuberculosis (TB) is a reemerging disease that remains as a leading cause of morbidity and mortality in humans. To identify and characterize a T-cell epitope suitable for vaccine design, we have utilized the Vaxign server to assess all antigenic proteins ofMycobacteriumspp. recorded to date in the Protegen database. We found that the extracellular protein 85B displayed the most robust antigenicity among the proteins identified. Computational tools for identifying T-cell epitopes predicted an epitope, 181-QQFIYAGSLSALLDP-195, that could bind to at least 13 major histocompatibility complexes, revealing the promiscuous nature of the epitope. Molecular docking simulation demonstrated that the epitope could bind to the binding groove of MHC II and MHC I molecules by several hydrogen bonds. Molecular docking analysis further revealed that the epitope had a distinctive binding pattern to all DRB1 and A and B series of MHC molecules and presented almost no polymorphism in its binding site. Moreover, using “Allele Frequency Database,” we checked the frequency of HLA alleles in the worldwide population and found a higher frequency of both class I and II HLA alleles in individuals living in TB-endemic regions. Our results indicate that the identified peptide might be a universal candidate to produce an efficient epitope-based vaccine for TB.

scholarly journals Identification of T-cell epitopes in the structural and non-structural proteins of classical swine fever virus

2002 ◽  
Vol 83 (3) ◽  
pp. 551-560 ◽  
Author(s):  
Elisenda Armengol ◽  
Karl-Heinz Wiesmüller ◽  
Daniel Wienhold ◽  
Mathias Büttner ◽  
Eberhard Pfaff ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Classical Swine Fever Virus ◽  
Cell Epitope ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Target Cells ◽  
T Cell Epitopes ◽  
Structural Protein

To identify new T-cell epitopes of classical swine fever virus (CSFV), 573 overlapping, synthetic pentadecapeptides spanning 82% of the CSFV (strain Glentorf) genome sequence were synthesized and screened. In proliferation assays, 26 peptides distributed throughout the CSFV viral protein sequences were able to induce specific T-cell responses in PBMCs from a CSFV-Glentorf-infected d/d haplotype pig. Of these 26 peptides, 18 were also recognized by PBMCs from a CSFV-Alfort/187-infected d/d haplotype pig. In further experiments, it could be shown that peptide 290 (KHKVRNEVMVHWFDD), which corresponds to amino acid residues 1446–1460 of the CSFV non-structural protein NS2–3 could induce interferon-γ secretion after secondary in vitro restimulation. The major histocompatibility complex (MHC) restriction for stimulation of T-cells by this pentadecapeptide was identified as being mainly MHC class II and partially MHC class I. In cytolytic assays, CSFV-specific cytotoxic T-lymphocytes (CTLs) were able to lyse peptide 290-loaded target cells. These findings indicate the existence of a CSFV-specific helper T-cell epitope and a CTL epitope in this peptide.

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