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 Cytotoxic T-Lymphocyte Elicited Vaccine against SARS-CoV-2 employing Immunoinformatics Framework

2020 ◽  
Author(s):  
Neeraj Kumar ◽  
Nikita Admane ◽  
Anchala Kumari ◽  
Damini Sood ◽  
Sonam Grover ◽  
...  
Keyword(s):  
Cytotoxic T Lymphocyte ◽  
Dynamics Simulation ◽  
Cytotoxic T Cell ◽  
Immunological Parameters ◽  
Robust Immune Response ◽  
Strong Binding ◽  
Viral Vaccine ◽  
Novel Coronavirus

Abstract Development of effective counteragents against the novel coronavirus disease caused by SARS CoV-2 strains requires clear insights for understanding immune responses associated with it. The succumbing of available therapeutics utterly warrants the development of a potential vaccine to contest the deadly situation. Herein, we report Cytotoxic T-cell Lymphocytes immunomodulator by advanced immunoinformatics avenues for spike-glycoprotein of SARS CoV-2, which can generate robust immune response with convincing immunological parameters (Antigenicity, TAP affinity, MHC-binder) engendering an efficient viral vaccine. Strong binding of the CTL construct with MHC-1 and membrane-specific TLR2 was conferred through molecular docking and molecular dynamics simulation in an explicit system. 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 0.4nm. The reduced Rg value (3.3nm) and stagnant SASA analysis (275nm/S2/N after 8ns and 5ns) for protein surface and its orientation in exposed and buried regions suggests more compactness by strong binding of epitope. The CTL vaccine candidate establishes a high capability to elicit critical immune regulators, like T-cells and memory cells as proven by in silico immunization assays and can be further corroborated through in vitro and in vivo assays.

scholarly journals Gag-Positive Reservoir Cells Are Susceptible to HIV-Specific Cytotoxic T Lymphocyte Mediated Clearance In Vitro and Can Be Detected In Vivo

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e71879 ◽  
Author(s):  
Erin H. Graf ◽  
Matthew J. Pace ◽  
Bennett A. Peterson ◽  
Lindsay J. Lynch ◽  
Steve B. Chukwulebe ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte

scholarly journals Heat Shock Protein–Peptide Complexes, Reconstituted In Vitro, Elicit Peptide-specific Cytotoxic T Lymphocyte Response and Tumor Immunity

1997 ◽  
Vol 186 (8) ◽  
pp. 1315-1322 ◽  
Author(s):  
Nathalie E. Blachere ◽  
Zihai Li ◽  
Rajiv Y. Chandawarkar ◽  
Ryuichiro Suto ◽  
Navdeep S. Jaikaria ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
T Lymphocyte ◽  
Synthetic Peptides ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Response ◽  
Lymphocyte Response ◽  
Peptide Complexes

Heat shock protein (HSP) preparations derived from cancer cells and virus-infected cells have been shown previously to elicit cancer-specific or virus-specific immunity. The immunogenicity of HSP preparations has been attributed to peptides associated with the HSPs. The studies reported here demonstrate that immunogenic HSP–peptide complexes can also be reconstituted in vitro. The studies show that (a) complexes of hsp70 or gp96 HSP molecules with a variety of synthetic peptides can be generated in vitro; (b) the binding of HSPs with peptides is specific in that a number of other proteins tested do not bind synthetic peptides under the conditions in which gp96 molecules do; (c) HSP–peptide complexes reconstituted in vitro are immunologically active, as tested by their ability to elicit antitumor immunity and specific CD8+ cytolytic T lymphocyte response; and (d) synthetic peptides reconstituted in vitro with gp96 are capable of being taken up and re-presented by macrophage in the same manner as gp96– peptides complexes generated in vivo. These observations demonstrate that HSPs are CD8+ T cell response–eliciting adjuvants.

scholarly journals Phloroglucinol as a Potential Candidate against Trypanosoma congolense Infection: Insights from In Vivo, In Vitro, Molecular Docking and Molecular Dynamic Simulation Analyses

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 469
Author(s):  
Nasirudeen Idowu Abdulrashid ◽  
Suleiman Aminu ◽  
Rahma Muhammad Adamu ◽  
Nasir Tajuddeen ◽  
Murtala Bindawa Isah ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Binding Energies ◽  
Sub Saharan Africa ◽  
Dynamics Simulation ◽  
Potential Candidate ◽  
Inhibitory Effects ◽  
Hydrogen Bond Interaction

Sub-Saharan Africa is profoundly challenged with African Animal Trypanosomiasis and the available trypanocides are faced with drawbacks, necessitating the search for novel agents. Herein, the chemotherapeutic potential of phloroglucinol on T. congolense infection and its inhibitory effects on the partially purified T. congolense sialidase and phospholipase A2 (PLA2) were investigated. Treatment with phloroglucinol for 14 days significantly (p < 0.05) suppressed T. congolense proliferation, increased animal survival and ameliorated anemia induced by the parasite. Using biochemical and histopathological analyses, phloroglucinol was found to prevent renal damages and splenomegaly, besides its protection against T. congolense-associated increase in free serum sialic acids in infected animals. Moreover, the compound inhibited bloodstream T. congolense sialidase via mixed inhibition pattern with inhibition binding constant (Ki) of 0.181 µM, but a very low uncompetitive inhibitory effects against PLA2 (Ki > 9000 µM) was recorded. Molecular docking studies revealed binding energies of −4.9 and −5.3 kcal/mol between phloroglucinol with modeled sialidase and PLA2 respectively, while a 50 ns molecular dynamics simulation using GROMACS revealed the sialidase-phloroglucinol complex to be more compact and stable with higher free binding energy (−67.84 ± 0.50 kJ/mol) than PLA2-phloroglucinol complex (−77.17 ± 0.52 kJ/mol), based on MM-PBSA analysis. The sialidase-phloroglucinol complex had a single hydrogen bond interaction with Ser453 while none was observed for the PLA2-phloroglucinol complex. In conclusion, phloroglucinol showed moderate trypanostatic activity with great potential in ameliorating some of the parasite-induced pathologies and its anti-anemic effects might be linked to inhibition of sialidase rather than PLA2.

scholarly journals Anthrax Toxin-Mediated Delivery In Vivo and In Vitro of a Cytotoxic T-Lymphocyte Epitope from Ovalbumin

1998 ◽  
Vol 66 (2) ◽  
pp. 615-619 ◽  
Author(s):  
Jimmy D. Ballard ◽  
Amy M. Doling ◽  
Kathryn Beauregard ◽  
R. John Collier ◽  
Michael N. Starnbach
Keyword(s):  
Fusion Protein ◽  
T Lymphocyte ◽  
Self Assembly ◽  
Protective Antigen ◽  
Cytotoxic T Lymphocyte ◽  
Ex Vivo ◽  
Lethal Factor ◽  
Anthrax Toxin

ABSTRACT We reported earlier that a nontoxic form of anthrax toxin was capable of delivering a cytotoxic T-lymphocyte (CTL) epitope in vivo, such that a specific CTL response was primed against the epitope. The epitope, of bacterial origin, was fused to an N-terminal fragment (LFn) from the lethal-factor component of the toxin, and the fusion protein was injected, together with the protective antigen (PA) component, into BALB/c mice. Here we report that PA plus LFn is capable of delivering a different epitope—OVA257–264 from ovalbumin. Delivery was accomplished in a different mouse haplotype,H-2Kb and occurred in vitro as well as in vivo. An OVA257–264-specific CTL clone, GA-4, recognized EL-4 cells treated in vitro with PA plus as little as 30 fmol of the LFn-OVA257–264 fusion protein. PA mutants attenuated in toxin self-assembly or translocation were inactive, implying that the role of PA in epitope delivery is the same as that in toxin action. Also, we showed that OVA257–264-specific CTL could be induced to proliferate by incubation with splenocytes treated with PA plus LFn-OVA257–264. These findings imply that PA-LFn may serve as a general delivery vehicle for CTL epitopes in vivo and as a safe, efficient tool for the ex vivo expansion of patient-derived CTL for use in adoptive immunotherapy.

scholarly journals Use of a High-Affinity Peptide That Aborts MHC-Restricted Cytotoxic T Lymphocyte Activity against Multiple Viruses in Vitro and Virus-Induced Immunopathologic Disease in Vivo

Virology ◽  
1999 ◽  
Vol 256 (2) ◽  
pp. 246-257 ◽  
Author(s):  
Michael B.A. Oldstone ◽  
Matthias von Herrath ◽  
Hanna Lewicki ◽  
Denis Hudrisier ◽  
J.Lindsay Whitton ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
High Affinity ◽  
Lymphocyte Activity ◽  
Affinity Peptide

scholarly journals Accelerated tumor growth in mice deficient in DNAM-1 receptor

2008 ◽  
Vol 205 (13) ◽  
pp. 2959-2964 ◽  
Author(s):  
Akiko Iguchi-Manaka ◽  
Hirayasu Kai ◽  
Yumi Yamashita ◽  
Kai Shibata ◽  
Satoko Tahara-Hanaoka ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Nk Cell ◽  
Cytotoxic T Lymphocyte ◽  
Immune Surveillance ◽  
Tumor Development ◽  
Wild Type ◽  
Human And Mouse ◽  
Deficient Mice

Since the identification of ligands for human and mouse DNAM-1, emerging evidence has suggested that DNAM-1 plays an important role in the T cell– and natural killer (NK) cell–mediated recognition and lysis of tumor cells. However, it remains undetermined whether DNAM-1 is involved in tumor immune surveillance in vivo. We addressed this question by using DNAM-1–deficient mice. DNAM-1–deficient cytotoxic T lymphocyte (CTL) and NK cells showed significantly less cytotoxic activity against DNAM-1 ligand-expressing tumors in vitro than wild-type (WT) cells. The methylcholanthrene (MCA)-induced fibrosarcoma cell line Meth A expressed the DNAM-1 ligand CD155, and DNAM-1–deficient mice showed increased tumor development and mortality after transplantation of Meth A cells. Moreover, the DNAM-1–deficient mice developed significantly more DNAM-1 ligand-expressing fibrosarcoma and papilloma cells in response to the chemical carcinogens MCA and 7,12-dimethylbenz[a]anthracene (DMBA), respectively, than did WT mice. These results indicate that DNAM-1 plays an important role in immune surveillance of tumor development.

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