Towards A Novel Multi-Epitopes Chimeric Vaccine for Simulating Strong Immune Responses and Protection against
Asad Ullah1, Sajjad Ahmad1, Saba Ismail2
1Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan.
Abstract:
Morganella morganii is one of the main etiological agents of hospital-acquired infections and no licensed vaccine is available against the pathogen. Herein, we designed a multi-epitope-based vaccine against M. morganii. Predicted proteins from fully sequenced genomes of the pathogen were subjected to a core sequences analysis, followed by the prioritization of non-redundant, host non-homologous and extracellular, outer membrane and periplasmic membrane virulent proteins as vaccine targets. Five proteins (TonB-dependent siderophore receptor, serralysin family metalloprotease, type 1 fimbrial protein, flagellar hook protein (FlgE), and pilus periplasmic chaperone) were shortlisted for the epitope prediction. The predicted epitopes were checked for antigenicity, toxicity, solubility, and binding affinity with the DRB*0101 allele. The selected epitopes were linked with each other through GPGPG linkers and were joined with the cholera toxin B subunit (CTBS) to boost immune responses. The tertiary structure of the vaccine was modeled and blindly docked with MHC-I, MHC-II, and Toll-like receptors 4 (TLR4). Molecular dynamic simulations of 250 nanoseconds affirmed that the designed vaccine showed stable conformation with the receptors. Further, intermolecular binding free energies demonstrated the domination of both the van der Waals and electrostatic energies. Overall, the results of the current study might help experimentalists to develop a novel vaccine against M. morganii.
Insights
Researchers designed a novel multi-epitope vaccine targeting hospital-acquired infections caused by Morganella morganii. This computational study paves the way for developing a much-needed vaccine against this challenging pathogen.
Area of Science:
- Vaccinology
- Computational vaccinology
- Infectious disease research
Background:
- Morganella morganii is a significant cause of hospital-acquired infections.
- Currently, no licensed vaccine is available for M. morganii.
- Effective vaccine development strategies are crucial for combating this pathogen.
Purpose of the Study:
- To design a novel multi-epitope-based vaccine against Morganella morganii.
- To computationally evaluate the potential efficacy and stability of the designed vaccine.
- To provide a foundation for experimental vaccine development.
Main Methods:
- In silico analysis of M. morganii virulent proteins for epitope identification.
- Epitope selection based on antigenicity, toxicity, solubility, and MHC binding.
- Vaccine construct design using linkers and cholera toxin B subunit (CTBS), followed by molecular modeling, docking, and molecular dynamic simulations.
Main Results:
- Five key proteins were identified as vaccine targets, and relevant epitopes were predicted.
- The designed multi-epitope construct showed stable conformation and strong binding affinity with MHC and TLR4 receptors.
- Molecular dynamics simulations confirmed the stability of the vaccine-receptor complexes.
Conclusions:
- The in silico designed multi-epitope vaccine demonstrates promising potential against Morganella morganii.
- The study provides a strong theoretical basis for the experimental development of a novel M. morganii vaccine.
- This approach could accelerate the development of vaccines against other challenging bacterial pathogens.
