scholarly journals Immunoinformatic based identification of cytotoxic T lymphocyte epitopes from the Indian isolate of SARS-CoV-2

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Viswajit Mulpuru ◽  
Nidhi Mishra
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Human Leukocyte ◽  
Docking Studies ◽  
Indian Isolate ◽  
Dynamics Simulation ◽  
Effective Vaccine ◽  
Ctl Epitopes ◽  
Hla System ◽  
Epitope Candidate

AbstractThe Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has turned into a pandemic with about thirty million confirmed cases worldwide as of September 2020. Being an airborne infection, it can be catastrophic to populous countries like India. This study sets to identify potential cytotoxic T lymphocyte (CTL) epitopes in the SARS-CoV-2 Indian isolate which can act as an effective vaccine epitope candidate for the majority of the Indian population. The immunogenicity and the foreignness of the epitopes towards the human body have to be studied to further confirm their candidacy. The top-scoring epitopes were subjected to molecular docking studies to study their interactions with the corresponding human leukocyte antigen (HLA) system. The CTL epitopes were observed to bind at the peptide-binding groove of the corresponding HLA system, indicating their potency as an epitope candidate. The candidacy was further analyzed using sequence conservation studies and molecular dynamics simulation. The identified epitopes can be subjected to further studies for the development of the SARS-CoV-2 vaccine.

scholarly journals Immunoinformatic based identification of cytotoxic T lymphocyte epitopes from the Indian isolate of SARS-CoV-2

2020 ◽  
Author(s):  
Viswajit Mulpuru ◽  
Nidhi Mishra
Keyword(s):  
T Lymphocyte ◽  
Vaccine Candidate ◽  
Cytotoxic T Lymphocyte ◽  
Human Leukocyte ◽  
Docking Studies ◽  
Indian Isolate ◽  
Effective Vaccine ◽  
Ctl Epitopes ◽  
Hla System ◽  
Peptide Binding Groove

Abstract The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has turned into a pandemic with about a million confirmed cases worldwide. Being an airborne infection, it can be highly fatal to populous countries like India. This study sets to identify potential cytotoxic T lymphocyte (CTL) epitopes in the SARS-CoV-2 Indian isolate which can acts act as an effective vaccine candidate for the majority of the Indian population. The immunogenicity and the foreignness of the epitopes towards the human body have to studies to further confirm their candidacy. The top-scoring epitopes were subjected to molecular docking studies to study their interactions with the corresponding human leukocyte antigen (HLA) system. The CTL epitopes were observed to bind at the peptide-binding groove of the corresponding HLA system, indicating their potency as a vaccine candidate. The identified epitopes can be subjected to further studies for the development of SARS-CoV-2 vaccine.

scholarly journals Cytotoxic T-lymphocyte elicited vaccine against SARS-CoV-2 employing immunoinformatics framework

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Neeraj Kumar ◽  
Nikita Admane ◽  
Anchala Kumari ◽  
Damini Sood ◽  
Sonam Grover ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Docking Studies ◽  
Dynamics Simulation ◽  
Binding Interaction ◽  
Immunological Parameters ◽  
Strong Binding ◽  
Viral Vaccine

AbstractDevelopment of effective counteragents against the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, requires clear insights and information for understanding the immune responses associated with it. This global pandemic has pushed the healthcare system and restricted the movement of people and succumbing of the available therapeutics utterly warrants the development of a potential vaccine to contest the deadly situation. In the present study, highly efficacious, immunodominant cytotoxic T-lymphocyte (CTL) epitopes were predicted by advanced immunoinformatics assays using the spike glycoprotein of SARS-CoV2, generating a robust and specific immune response with convincing immunological parameters (Antigenicity, TAP affinity, MHC binder) engendering an efficient viral vaccine. The molecular docking studies show strong binding of the CTL construct with MHC-1 and host membrane specific TLR2 receptors. The molecular dynamics simulation in an explicit system confirmed the stable and robust binding of CTL epitope with TLR2. Steep magnitude RMSD variation and compelling residual fluctuations existed in terminal residues and various loops of the β linker segments of TLR2-epitope (residues 105-156 and 239-254) to about 0.4 nm. The reduced Rg value (3.3 nm) and stagnant SASA analysis (275 nm/S2/N after 8 ns and 5 ns) for protein surface and its orientation in the exposed and buried regions suggests more compactness due to the strong binding interaction of the epitope. The CTL vaccine candidate establishes a high capability to elicit the critical immune regulators, like T-cells and memory cells as proven by the in silico immunization assays and can be further corroborated through in vitro and in vivo assays.

scholarly journals Computational Mapping of Cytotoxic T Lymphocyte epitopes of Mycobacterium Tuberculosis and their Potential Role in Vaccine Design

2021 ◽  
Author(s):  
Esakkimuthu Thangamariappan ◽  
Manikandan Mohan ◽  
Krishnan Sundar
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Lymphocyte ◽  
Potential Role ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
Multiple Allele ◽  
Ctl Epitopes ◽  
Cell Mediated Immune Response

Objective: Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) is one of the deadliest diseases causing millions of deaths worldwide. Bacillus Calmette-Guérin (BCG) is the only vaccine that has been used in many countries where TB is prevalent. Despite vaccination, this disease prevails in many of the developing countries, necessitating the development of an effective vaccine against TB. Since M. tb acts as an intracellular pathogen, cell-mediated immune response plays an important role in disease control. Therefore, screening of CD8+ T cell epitopes of M. tb antigens could aid in the development of an effective vaccine against TB. In the current study, a reverse vaccinology approach was utilized to predict and map cytotoxic T lymphocyte (CTL) epitopes in the virulent proteins that are also essential for M. tb. Materials and Methods: Database of Essential Genes and Virulence Factor Database were used for identifying the virulent proteins of M. tb and their antigenicity was assessed using VaxiJen server. Various immunoinformatics tools were used to predict MHC class I binding, MHC processing, immunogenicity, toxicity and allergenicity. Results: Twelve M. tb antigens were selected for the prediction analyses using various tools. The results indicated the presence of 20 novel CTL epitopes predicted against human HLA-A alleles. This study has also screened for multiple allele binding epitopes that could be used as a vaccine component. Conclusion: This study has yielded a few hitherto unreported CTL epitopes binding to class I HLA-A alleles. Further experimental validation is necessary for confirming their potential as vaccine candidates.

scholarly journals Exploring the structural basis to develop efficient multi-epitope vaccines displaying interaction with HLA and TAP and TLR3 molecules to prevent NIPAH infection, a global threat to human health

2021 ◽  
Author(s):  
Sukrit Srivastava ◽  
Ajay Kumar Saxena ◽  
Michael Kolbe
Keyword(s):  
Immune Response ◽  
B Cell ◽  
T Lymphocyte ◽  
Antigen Processing ◽  
Dynamics Simulation ◽  
Structural Basis ◽  
Effective Vaccine ◽  
Mammalian Host ◽  
Ctl Epitopes ◽  
Epitope Vaccines

Nipah virus (NiV) is an emerging zoonotic virus responsible to cause several serious outbreaks in South Asian region with high mortality rate of 40 to 90% since 2001. NiV infection causes lethal encephalitis and respiratory disease with the symptom of endothelial cell-cell fusion. No specific vaccine has yet been reported against NiV infection. Recently, some Multi-Epitope Vaccines (MEV) has been proposed but they involve limited number of epitopes which further limits the potential of vaccine. To address the urgent need for a specific and effective vaccine against NiV infection, in the present study, we have design two multi-epitope vaccines (MEVs) composed of 33 Cytotoxic T lymphocyte (CTL) epitopes and 38 Helper T lymphocyte (HTL) epitopes. Both the MEVs carry potential B cell linear epitope overlapping regions, B cell discontinuous epitopes as well as IFN-γ inducing epitopes. Hence the designed MEVs carry potential to elicit cell-mediated as well as humoral immune response. Selected CTL and HTL epitopes were validated for their stable molecular interactions with HLA class I and II alleles as well as in case of CTL epitopes, with human transporter associated with antigen processing (TAP). Human β-defensin 2 and β-defensin 3 were used as adjuvants to enhance the immune response of both the MEVs. The molecular dynamics simulation study of MEVs-TLR3(ECD) (Toll-Like Receptor 3 Ectodomain) complex indicated stable molecular interaction. Further, the codon optimized cDNA of both the MEVs has shown high expression potential in the mammalian host cell line (Human). Hence for further studies, both the design of CTL and HTL MEVs could be cloned, expressed and tried for in-vivo validations (animal trails) as potential vaccine candidates against NiV infection.

scholarly journals Rational Design of a Pan-Coronavirus Vaccine Based on Conserved CTL Epitopes

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 333
Author(s):  
Minchao Li ◽  
Jinfeng Zeng ◽  
Ruiting Li ◽  
Ziyu Wen ◽  
Yanhui Cai ◽  
...  
Keyword(s):  
Public Health ◽  
Genetic Algorithm ◽  
T Lymphocyte ◽  
Rational Design ◽  
Cytotoxic T Lymphocyte ◽  
Biomedical Science ◽  
Effective Vaccine ◽  
Ctl Epitopes ◽  
Global Spread ◽  
Human Coronaviruses

With the rapid global spread of the Coronavirus Disease 2019 (COVID-19) pandemic, a safe and effective vaccine against human coronaviruses (HCoVs) is believed to be a top priority in the field of public health. Due to the frequent outbreaks of different HCoVs, the development of a pan-HCoVs vaccine is of great value to biomedical science. The antigen design is a key prerequisite for vaccine efficacy, and we therefore developed a novel antigen with broad coverage based on the genetic algorithm of mosaic strategy. The designed antigen has a potentially broad coverage of conserved cytotoxic T lymphocyte (CTL) epitopes to the greatest extent, including the existing epitopes from all reported HCoV sequences (HCoV-NL63, HCoV-229E, HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2). This novel antigen is expected to induce strong CTL responses with broad coverage by targeting conserved epitopes against multiple coronaviruses.

scholarly journals Efficient Identification of Novel Hla-A*0201–Presented Cytotoxic T Lymphocyte Epitopes in the Widely Expressed Tumor Antigen Prame by Proteasome-Mediated Digestion Analysis

2001 ◽  
Vol 193 (1) ◽  
pp. 73-88 ◽  
Author(s):  
Jan H. Kessler ◽  
Nico J. Beekman ◽  
Sandra A. Bres-Vloemans ◽  
Pauline Verdijk ◽  
Peter A. van Veelen ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Epitope Prediction ◽  
Binding Prediction ◽  
Ctl Epitopes ◽  
High Affinity ◽  
Tumor Associated Antigen ◽  
Immunotherapy Of Cancer ◽  
Binding Peptides

We report the efficient identification of four human histocompatibility leukocyte antigen (HLA)-A*0201–presented cytotoxic T lymphocyte (CTL) epitopes in the tumor-associated antigen PRAME using an improved “reverse immunology” strategy. Next to motif-based HLA-A*0201 binding prediction and actual binding and stability assays, analysis of in vitro proteasome-mediated digestions of polypeptides encompassing candidate epitopes was incorporated in the epitope prediction procedure. Proteasome cleavage pattern analysis, in particular determination of correct COOH-terminal cleavage of the putative epitope, allows a far more accurate and selective prediction of CTL epitopes. Only 4 of 19 high affinity HLA-A*0201 binding peptides (21%) were found to be efficiently generated by the proteasome in vitro. This approach avoids laborious CTL response inductions against high affinity binding peptides that are not processed and limits the number of peptides to be assayed for binding. CTL clones induced against the four identified epitopes (VLDGLDVLL, PRA100–108; SLYSFPEPEA, PRA142–151; ALYVDSLFFL, PRA300–309; and SLLQHLIGL, PRA425–433) lysed melanoma, renal cell carcinoma, lung carcinoma, and mammary carcinoma cell lines expressing PRAME and HLA-A*0201. This indicates that these epitopes are expressed on cancer cells of diverse histologic origin, making them attractive targets for immunotherapy of cancer.

scholarly journals Enhanced immune activity of cytotoxic T-lymphocyte epitope analogs derived from positional scanning synthetic combinatorial libraries

Blood ◽  
2001 ◽  
Vol 97 (6) ◽  
pp. 1776-1786 ◽  
Author(s):  
Corinna La Rosa ◽  
Radhika Krishnan ◽  
Susan Markel ◽  
Jonathan P. Schneck ◽  
Richard Houghten ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Combinatorial Libraries ◽  
Peptide Sequence ◽  
Ctl Epitopes ◽  
Ctl Epitope ◽  
Positional Scanning ◽  
Synthetic Combinatorial Libraries

The pp65495-503 cytotoxic T-lymphocyte (CTL) epitope from cytomegalovirus (CMV) is universally recognized among CMV+ individuals who express an allele of the human leukocyte antigen A (HLA-A*0201). The relative binding affinity of the epitope to HLA-A*0201 is moderate, and its increased activity might prove beneficial in its use as a CTL epitope vaccine. A new approach to enhance the activity of T-cell epitopes is the use of positional scanning synthetic combinatorial libraries (PS-SCLs). Using a nonamer PS-SCL, the pp65495-503 epitope was modified after screening a CMV-specific T-cell clone (TCC) (3-3F4) from which the native peptide sequence was derived. Two peptides with amino acid substitutions at P1, P3, P7, and P8 are between 103 and 104 more active than the native epitope. Although the native CTL epitope terminates as a free acid, both tetrasubstituted peptides only function as CTL epitopes when the carboxyl terminus is amidated. Selective substitution of the native sequence based on PS-SCL screening results identified 3 amidated monosubstituted and disubstituted peptides that are better recognized than the native epitope by TCCs from a cohort expressing HLA-A*0201. In vitro stimulation of peripheral blood mononuclear cells with each of the peptide epitope analogs stimulated memory CTLs, which recognized CMV-infected targets among a high percentage of CMV+ individuals. Binding studies of peptide analogs with HLA-Ig (immunoglobulin) dimers and 2 different TCCs correlated with in vitro lysis results. These data suggest that increasing the activity of CTL epitopes while maintaining broad recognition is possible, which holds promise for vaccine development in infectious disease and cancer.

scholarly journals Fusogenic Liposome can be Used as an Effective Vaccine Carrier for Peptide Vaccination to Induce Cytotoxic T Lymphocyte (CTL) Response

2005 ◽  
Vol 28 (1) ◽  
pp. 192-193 ◽  
Author(s):  
Toshiki Sugita ◽  
Tomoaki Yoshikawa ◽  
Jian-Qing Gao ◽  
Mariko Shimokawa ◽  
Atushi Oda ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Effective Vaccine ◽  
Peptide Vaccination ◽  
Ctl Response ◽  
Vaccine Carrier

scholarly journals Cytotoxic T-Lymphocyte Epitope Vaccination Protects against Human Metapneumovirus Infection and Disease in Mice

2006 ◽  
Vol 80 (4) ◽  
pp. 2034-2044 ◽  
Author(s):  
Karen A. Herd ◽  
Suresh Mahalingam ◽  
Ian M. Mackay ◽  
Michael Nissen ◽  
Theo P. Sloots ◽  
...  
Keyword(s):  
Young Children ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Human Metapneumovirus ◽  
Respiratory Pathogen ◽  
Interleukin 12 ◽  
Ctl Epitopes ◽  
Ctl Epitope ◽  
Hmpv Infection ◽  
Tract Infections

ABSTRACT Human metapneumovirus (hMPV) has emerged as an important human respiratory pathogen causing upper and lower respiratory tract infections in young children and older adults. In addition, hMPV infection is associated with asthma exacerbation in young children. Recent epidemiological evidence indicates that hMPV may cocirculate with human respiratory syncytial virus (hRSV) and mediate clinical disease similar to that seen with hRSV. Therefore, a vaccine for hMPV is highly desirable. In the present study, we used predictive bioinformatics, peptide immunization, and functional T-cell assays to define hMPV cytotoxic T-lymphocyte (CTL) epitopes recognized by mouse T cells restricted through several major histocompatibility complex class I alleles, including HLA-A*0201. We demonstrate that peptide immunization with hMPV CTL epitopes reduces viral load and immunopathology in the lungs of hMPV-challenged mice and enhances the expression of Th1-type cytokines (gamma interferon and interleukin-12 [IL-12]) in lungs and regional lymph nodes. In addition, we show that levels of Th2-type cytokines (IL-10 and IL-4) are significantly lower in hMPV CTL epitope-vaccinated mice challenged with hMPV. These results demonstrate for the first time the efficacy of an hMPV CTL epitope vaccine in the control of hMPV infection in a murine model.

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