Designing a novel multi-epitope vaccine to evoke a robust immune response against pathogenic multidrug-resistant Enterococcus faecium bacterium

Gut Pathogens, Journal Year: 2022, Volume and Issue: 14(1)

Published: May 27, 2022

Enterococcus faecium is an emerging ESKAPE bacterium that capable of causing severe public health complications in humans. There are currently no licensed treatments or vaccinations to combat the deadly pathogen. We aimed design a potent and novel prophylactic chimeric vaccine against E. through immunoinformatics approach The antigenic Penicillin-binding protein 5 (PBP 5) was selected identify B T cell epitopes, followed by conservancy analysis, population coverage, physiochemical assessment, secondary tertiary structural analysis. Using various methods tools, two linear B-cell five CTL HTL epitopes were finally for development. constructed determined be highly immunogenic, cytokine-producing, antigenic, non-toxic, non-allergenic, stable, as well potentially effective faecium. In addition, disulfide engineering, codon adaptation, silico cloning, used improve stability expression efficiency host coli. Molecular docking molecular dynamics simulations indicated structure stable has high affinity TLR4 receptor. immune simulation results revealed both cells had increased response vaccination component. Conclusively, in-depth analysis suggests, proposed elicit robust infection hence promising target further experimental trials.

Language: Английский

---

Molecular Characterization and Designing of a Novel Multiepitope Vaccine Construct Against Pseudomonas aeruginosa

International Journal of Peptide Research and Therapeutics, Journal Year: 2022, Volume and Issue: 28(2)

Published: Jan. 17, 2022

Language: Английский

---

Designing of multi-epitope peptide vaccine against Acinetobacter baumannii through combined immunoinformatics and protein interaction–based approaches

Immunologic Research, Journal Year: 2023, Volume and Issue: 71(4), P. 639 - 662

Published: April 6, 2023

Language: Английский

---

ExploringKlebsiella pneumoniaecapsule polysaccharide proteins to design multiepitope subunit vaccine to fight against pneumonia

Expert Review of Vaccines, Journal Year: 2021, Volume and Issue: 21(4), P. 569 - 587

Published: Dec. 21, 2021

Klebsiella pneumoniae is an emerging human pathogen causing neonatal lung disease, catheter-associated infections, and nosocomial outbreaks with high fatality rates. Capsular polysaccharide (CPS) protein plays a major determinant in virulence considered as promising target for vaccine development.In this study, we used immunoinformatic approaches to design multi-peptide against K. pneumonia. The epitopes were selected through several immune filters, such antigenicity, conservancy, nontoxicity, non-allergenicity, binding affinity HLA alleles, overlapping epitopes, peptides having common epitopes.Finally, construct comprising 2 B-Cell, 8 CTL, HTL along adjuvant, linkers was designed. Peptide-HLA interaction analysis showed strong of these molecules. silico simulation population coverage the its potential evoke responses.. Further, between evaluated by docking simulation, revealing complex stability. Codon adaptation cloning revealed higher expression E. coli K12 system.Conclusively, findings present study suggest that designed novel multi-epitopic holds further experimental validation pathogen.

Language: Английский

---

Immunoinformatics-guided designing of epitope-based subunit vaccine from Pilus assembly protein of Acinetobacter baumannii bacteria

Journal of Immunological Methods, Journal Year: 2022, Volume and Issue: 508, P. 113325 - 113325

Published: July 28, 2022

Language: Английский

---

An integrative reverse vaccinology, immunoinformatic, docking and simulation approaches towards designing of multi-epitopes based vaccine against monkeypox virus

Journal of Biomolecular Structure and Dynamics, Journal Year: 2022, Volume and Issue: 41(16), P. 7821 - 7834

Published: Sept. 21, 2022

Monkeypox is a viral zoonotic disease that caused by the monkeypox virus (MPXV) and mainly transmitted to human through close contact with an infected person, animal, or fomites which contaminated virus. In present research work, reverse vaccinology several other bioinformatics immunoinformatics tools were utilized design multi-epitopes-based vaccine against MPXV exploring three probable antigenic extracellular proteins: cupin domain-containing protein, ABC transporter ATP-binding protein DUF192 protein. Both cellular humoral immunity induction main concerning qualities of construct, hence from selected proteins both B T-cells epitopes predicted. Antigenicity, allergenicity, toxicity, water solubility predicted assessed only antigenic, non-allergic, non-toxic good water-soluble used in multi-epitopes construct. The developed was found be potentially effective highly immunogenic, cytokine-producing, non-toxic, non-allergenic, stable. Additionally, increase stability expression efficiency host E. coli, disulfide engineering, codon adaptation, silico cloning employed. Molecular docking biophysical approaches evaluate binding mode dynamic behavior construct TLR-2, TLR-4, TLR-8. outcomes immune simulation demonstrated T cells responded more strongly vaccination component. detailed analysis concludes proposed will induce strong response infection, making it promising target for additional experimental trials.Communicated Ramaswamy H. Sarma.

Language: Английский

---

Designing a Next-Generation Multiepitope-Based Vaccine against Staphylococcus aureus Using Reverse Vaccinology Approaches

Pathogens, Journal Year: 2023, Volume and Issue: 12(3), P. 376 - 376

Published: Feb. 25, 2023

Staphylococcus aureus is a human bacterial pathogen that can cause wide range of symptoms. As virulent and multi-drug-resistant strains S. have evolved, invasive infections in hospitals the community become one leading causes mortality morbidity. The development novel techniques therefore necessary to overcome this infection. Vaccines are an appropriate alternative context control infections. In study, collagen-binding protein (CnBP) from was chosen as target antigen, series computational methods were used find epitopes may be vaccine systematic way. passed through filtering pipeline included antigenicity, toxicity, allergenicity, cytokine inducibility testing, with objective identifying capable eliciting both T B cell-mediated immune responses. To improve immunogenicity, final phenol-soluble modulin α4 adjuvant fused together using linkers; consequence, multiepitope developed. cell epitope ensemble expected cover 99.14% global population. Furthermore, docking dynamics simulations examine vaccine's interaction Toll-like receptor 2 (TLR2), revealing great affinity, consistency, stability between two. Overall, data indicate candidate extremely successful, it will need evaluated experimental systems confirm its efficiency.

Language: Английский

---

Development of a novel multi-epitope mRNA vaccine candidate to combat HMPV virus

Human Vaccines & Immunotherapeutics, Journal Year: 2024, Volume and Issue: 20(1)

Published: Jan. 3, 2024

Human metapneumovirus (HMPV) is one of the main pathogens causing severe respiratory infections in children, as a common cause immunodeficiency-related deaths children and elderly individuals, prevalence HMPV has been showing an increasing trend during last years. However, no vaccines or effective treatment plans are available currently. In this present, based on candidate proteins highly associated with viral virulence promising protective potential, we screened for immunodominant cytotoxic T cells, helper Linear B-cell epitopes from most Fusion protein, together G, SH, M, M2. All were predicted to have strong antigenicity by Vaxijen pose potential toxicity, allergenicity, hormonology human Toxinpred, Allerpred, Blast analysis, meanwhile, high conservancy demanded cover different subtypes. adjuvants β-defensin II Pam2Cys was attached EAAAK linkers improve vaccine's efficiency. Then, calculation physicochemical properties proved protein vaccine product can stably exist body. Besides, assessed docking between immune receptors evaluate its ability stimulate responses, dynamic simulation further confirmed that tightly bind receptors, which approved construction induce humoral cellular response. Finally, constructed into multi-epitope mRNA vaccine, simulations suggest controlling infection.

Language: Английский

---

A computational approach to design a multiepitope vaccine against H5N1 virus

Virology Journal, Journal Year: 2024, Volume and Issue: 21(1)

Published: March 20, 2024

Abstract Since 1997, highly pathogenic avian influenza viruses, such as H5N1, have been recognized a possible pandemic hazard to men and the poultry business. The rapid rate of mutation H5N1 viruses makes whole process designing vaccines extremely challenging. Here, we used an in silico approach design multi-epitope vaccine against A virus using hemagglutinin (HA) neuraminidase (NA) antigens. B-cell epitopes, Cytotoxic T lymphocyte (CTL) Helper (HTL) were predicted via IEDB, NetMHC-4 NetMHCII-2.3 respectively. Two adjuvants consisting Human β-defensin-3 (HβD-3) along with pan HLA DR-binding epitope (PADRE) chosen induce more immune response. Linkers including KK, AAY, HEYGAEALERAG, GPGPGPG double EAAAK utilized link epitopes adjuvants. This construct encodes protein having 350 amino acids 38.46 kDa molecular weight. Antigenicity ~ 1, allergenicity non-allergen, toxicity negative solubility appropriate confirmed through Vaxigen, AllerTOP, ToxDL DeepSoluE, 3D structure was refined validated Z-Score − 0.87 overall Ramachandran 99.7%. Docking analysis showed could interact TLR7 (docking score 374.08 by 4 hydrogen bonds) TLR8 414.39 3 bonds). Molecular dynamics simulations results RMSD RMSF 0.25 nm 0.2 for H5N1-TLR7 well 0.45 0.4 H5N1-TLR8 complexes, Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) stability continuity interaction between total binding energy 29.97 kJ/mol 23.9 kJ/mol. Investigating response simulation evidence ability stimulate B cells immunity system that shows merits this proposed candidate clinical trials.

Language: Английский

---

PAPreC: A Pipeline for Antigenicity Prediction Comparison Methods across Bacteria

ACS Omega, Journal Year: 2025, Volume and Issue: 10(6), P. 5415 - 5429

Published: Feb. 3, 2025

Antigenicity prediction plays a crucial role in vaccine development, antibody-based therapies, and diagnostic assays, as this predictive approach helps assess the potential of molecular structures to induce recruit immune cells drive antibody production. Several existing methods, which target complete proteins epitopes identified through reverse vaccinology, face limitations regarding input data constraints, feature extraction strategies, insufficient flexibility for model evaluation interpretation. This work presents PAPreC (Pipeline Prediction Comparison), an open-source, versatile workflow (available at https://github.com/YasCoMa/paprec_nx_workflow) designed address these challenges. systematically examines three key factors: selection training sets, methods (including physicochemical descriptors ESM-2 encoder-derived embeddings), diverse classifiers. It provides automated evaluation, interpretability SHapley Additive exPlanations (SHAP) analysis, applicability domain assessments, enabling researchers identify optimal configurations their specific sets. Applying IEDB reference, we demonstrate its effectiveness across ESKAPE pathogen group. A case study involving Pseudomonas aeruginosa Staphylococcus aureus shows that are more suitable different sequence types, embeddings enhance performance. Moreover, our results indicate separate models Gram-positive Gram-negative bacteria not required. offers comprehensive, adaptable, robust framework streamline improve antigenicity bacterial

Language: Английский

---