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Computational design of an mRNA vaccine targeting antifungal-resistant Lomentospora prolificans
Muhammad Bilal Iqbal Rehmani1, Fizza Arshad1, Muhammad Umer Khan2
1Department of Biochemistry, Bahauddin Zakariya University, Multan, 66000, Punjab, Pakistan.
Abstract:
Lomentospora prolificans is an emerging opportunistic pathogen that predominantly affects immunocompromised individuals, as well as healthy individuals, often leading to disseminated disease with high mortality rates. Effective treatment is challenging due to its high intrinsic resistance to antifungal agents. To address this, we employed subtractive proteomics and reverse vaccinology approaches to identify potential antigenic proteins for the design of an mRNA-based multi-epitope vaccine (MEV). Our study identified four antigenic proteins as promising vaccine targets. A vaccine construct was developed using a combination of twelve cytotoxic T lymphocyte (CTL), nine helper T lymphocyte (HTL), and five linear B lymphocyte (LBL) epitopes. These epitopes were connected using appropriate linkers (AAY, GPGPG, and KK) and adjuvants to enhance antigenicity and immunogenicity. The vaccine construct was rigorously evaluated for its physicochemical properties, demonstrating high antigenicity, non-toxicity, non-allergenicity, stability, and solubility. Molecular docking studies were conducted to validate the interactions between the vaccine construct and the human toll-like receptor (TLR4). Immune simulation studies further confirmed the vaccine's potential to elicit a robust immune response. Additionally, molecular dynamics (MD) simulations, principal component analysis (PCA), dynamic cross-correlation matrix (DCCM) analysis, and binding free energy calculations were performed to assess the stability and efficacy of the vaccine-receptor complex. Codon optimization and in-silico cloning were carried out to ensure efficient expression of the vaccine in Escherichia coli strain K12. The findings of this study suggest that the proposed vaccine construct holds significant promise as a novel mRNA-based therapeutic candidate against L. prolificans infections. Further experimental validation is recommended to advance this vaccine toward clinical application.
Insights
This study developed a novel mRNA-based multi-epitope vaccine (MEV) targeting Lomentospora prolificans, an opportunistic fungal pathogen. In silico analysis shows promising potential for a new therapeutic against resistant infections.
Area of Science:
- Mycology
- Immunology
- Vaccine Development
Background:
- Lomentospora prolificans is an opportunistic pathogen causing disseminated disease with high mortality.
- Antifungal resistance makes L. prolificans infections difficult to treat effectively.
Purpose of the Study:
- To design and evaluate a novel mRNA-based multi-epitope vaccine (MEV) against Lomentospora prolificans.
- To identify potential antigenic targets and epitopes for vaccine development.
Main Methods:
- Subtractive proteomics and reverse vaccinology were used to identify vaccine targets.
- Epitopes (CTL, HTL, LBL) were selected, linked, and assembled into a vaccine construct.
- In silico methods including molecular docking, MD simulations, and expression analysis were performed.
Main Results:
- Four antigenic proteins were identified as promising vaccine targets.
- The MEV construct demonstrated favorable physicochemical properties, high antigenicity, and stability.
- In silico studies predicted a robust immune response and stable vaccine-receptor complex.
Conclusions:
- The proposed mRNA-based MEV is a promising therapeutic candidate against L. prolificans infections.
- Further experimental validation is recommended for clinical advancement.
