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Designing a multi-epitope mRNA vaccine to combat human metapneumovirus based on consensus sequence using reverse
Ajay Kumar Singhmar1, Vinod Goyal2, Santosh Kumari3
1Department of Biotechnology, Guru Jambheshwar University of Science & Technology, Hisar, Haryana, 125001, India.
Abstract:
Human metapneumovirus (HMPV) ranks among the chief causes of serious respiratory illness in young children, accounting for about 3-10% of hospital admissions for acute lower respiratory tract infections in those under five years of age. Despite recent outbreaks and its rising incidence in recent years, no licensed vaccines or targeted therapies are currently available. In this study, surface viral proteins were selected as antigenic candidates, and their consensus sequences were derived from 782 HMPV genomes. Then using immunoinformatic approaches, immunodominant CTL, HTL, LBL epitopes within these proteins consensus sequence that exhibited high antigenicity, exhibiting no toxicity, no allergenic potential, and broad conservancy across HMPV clades were identified and combined with adjuvants, the PADRE sequence, and linkers for vaccine development. Physicochemical analysis confirmed that the resulting multi-epitope mRNA vaccine is stable under physiological conditions. Molecular docking analyses revealed robust interactions with important immune receptors and subsequent molecular dynamics simulations validated the stability of these complexes over time. Immune simulations predicted robust humoral and cellular responses. Finally, a Kozak sequence was included to enhance mRNA stability and translational efficiency, followed by an MITD sequence to enhance epitope presentation, a TAA codon to terminate translation, and for stability 5' UTR and 3' UTR was added and the engineered mRNA's secondary structure was predicted. Additionally final vaccine construct was cloned in silico into the pVAX1 vector, and virtual agarose gel electrophoresis was performed. These results support the potential of our multi-epitope mRNA vaccine as a promising preventive strategy against HMPV infection.
Insights
A novel multi-epitope mRNA vaccine was designed using immunoinformatics to target Human metapneumovirus (HMPV), a leading cause of respiratory illness in children. This vaccine candidate shows promise for preventing HMPV infections.
Area of Science:
- Vaccinology
- Immunoinformatics
- Molecular Biology
Background:
- Human metapneumovirus (HMPV) is a significant cause of severe respiratory illness in young children, leading to numerous hospital admissions.
- Currently, there are no licensed vaccines or specific therapies available for HMPV infection, highlighting an urgent need for preventive strategies.
Purpose of the Study:
- To design and computationally evaluate a novel multi-epitope mRNA vaccine against Human metapneumovirus (HMPV).
- To identify conserved, non-toxic, and non-allergenic viral epitopes for vaccine development.
Main Methods:
- Consensus sequences of HMPV surface proteins were derived from 782 genomes.
- Immunoinformatic approaches were used to identify immunodominant T-cell and B-cell epitopes.
- Epitopes were combined with adjuvants and linked into a multi-epitope construct for mRNA vaccine design.
- In silico analyses included physicochemical stability, molecular docking, molecular dynamics, immune simulations, mRNA secondary structure prediction, and cloning into a pVAX1 vector.
Main Results:
- Identified conserved, antigenic, non-toxic, and non-allergenic epitopes across HMPV clades.
- The designed multi-epitope mRNA vaccine construct demonstrated stability under physiological conditions.
- In silico analyses predicted robust humoral and cellular immune responses, stable interactions with immune receptors, and efficient mRNA translation.
- The final vaccine construct was successfully cloned in silico into the pVAX1 vector.
Conclusions:
- The developed multi-epitope mRNA vaccine is a promising candidate for preventing Human metapneumovirus (HMPV) infections.
- Computational validation supports the potential efficacy and stability of this novel vaccine strategy.
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