Decrypting the multi-genome data for chimeric vaccine designing against the antibiotic resistant Yersinia pestis
Asifa Sarfraz1, Sayyada Qurrat-Ul-Ain Fatima1, Muhammad Shehroz2
1Department of Biochemistry, Bahauddin Zakariya University, Multan 66000, Pakistan.
Abstract:
Yersinia pestis, the causative agent of plague, is a gram-negative bacterium that can be fatal if not treated properly. Three types of plague are currently known: bubonic, septicemic, and pneumonic plague, among which the fatality rate of septicemic and pneumonic plague is very high. Bubonic plague can be treated, but only if antibiotics are used at the initial stage of the infection. But unfortunately, Y. pestis has also shown resistance to certain antibiotics such as kanamycin, minocycline, tetracycline, streptomycin, sulfonamides, spectinomycin, and chloramphenicol. Despite tremendous progress in vaccine development against Y. pestis, there is no proper FDA-approved vaccine available to protect people from its infections. Therefore, effective broad-spectrum vaccine development against Y. pestis is indispensable. In this study, vaccinomics-assisted immunoinformatics techniques were used to find possible vaccine candidates by utilizing the core proteome prepared from 58 complete genomes of Y. pestis. Human non-homologous, pathogen-essential, virulent, and extracellular and membrane proteins are potential vaccine targets. Two antigenic proteins were prioritized for the prediction of lead epitopes by utilizing reverse vaccinology approaches. Four vaccine designs were formulated using the selected B- and T-cell epitopes coupled with appropriate linkers and adjuvant sequences capable of inducing potent immune responses. The HLA allele population coverage of the T-cell epitopes selected for vaccine construction was also analyzed. The V2 constructs were top-ranked and selected for further analysis on the basis of immunological, physicochemical, and immune-receptor docking interactions and scores. Docking and molecular dynamic simulations confirmed the stability of construct V2 interactions with the host immune receptors. Immune simulation analysis anticipated the strong immune profile of the prioritized construct. In silico restriction cloning ensured the feasible cloning ability of the V2 construct in the expression system of E. coli strain K12. It is anticipated that the designed vaccine construct may be safe, effective, and able to elicit strong immune responses against Y. pestis infections and may, therefore, merit investigation using in vitro and in vivo assays.
Insights
Developing a new vaccine against Yersinia pestis (plague) is crucial due to antibiotic resistance. This study used computational methods to design a promising multi-epitope vaccine construct, V2, showing potential for strong immune responses against plague.
Area of Science:
- Bacteriology
- Immunology
- Vaccinology
- Computational Biology
Background:
- Yersinia pestis causes plague, a potentially fatal disease with high mortality rates for septicemic and pneumonic forms.
- Antibiotic resistance in Y. pestis limits treatment options, and no FDA-approved vaccine is currently available.
- There is an urgent need for effective, broad-spectrum vaccines against Yersinia pestis infections.
Purpose of the Study:
- To identify potential vaccine candidates against Yersinia pestis using vaccinomics and immunoinformatics.
- To design and evaluate novel vaccine constructs with potent immunogenic properties.
Main Methods:
- Utilized vaccinomics and immunoinformatics on the core proteome of 58 Y. pestis genomes.
- Identified virulent, extracellular, and membrane proteins as vaccine targets.
- Employed reverse vaccinology to predict epitopes, formulate multi-epitope constructs (e.g., V2), and perform in silico analyses including molecular dynamics and docking simulations.
Main Results:
- Prioritized two antigenic proteins and designed four vaccine constructs, with V2 ranking highest based on immunological and physicochemical evaluations.
- Molecular simulations confirmed the stability and host immune receptor interaction of the V2 construct.
- Immune simulation predicted a strong immune response, and in silico cloning indicated feasibility for expression in E. coli.
Conclusions:
- The designed V2 vaccine construct shows promise as a safe and effective candidate against Yersinia pestis.
- Further in vitro and in vivo studies are warranted to validate the efficacy of the V2 construct.
