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Annotation of Potential Vaccine Targets and Designing of mRNA-Based Multi-Epitope Vaccine against Lumpy Skin Disease Virus via Reverse Vaccinology and Agent-Based Modeling

Lumpy skin disease is a fatal emerging disease of cattle, which has started to gain extensive attention due to its rapid incursions across the globe. The disease epidemic causes economic loss and cattle morbidity. Currently, there are no specific treatments and safe vaccines against the lumpy skin d...

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Detalles Bibliográficos
Autores principales: Kakakhel, Sehrish, Ahmad, Abbas, Mahdi, Wael A., Alshehri, Sultan, Aiman, Sara, Begum, Sara, Shams, Sulaiman, Kamal, Mehnaz, Imran, Mohd., Shakeel, Faiyaz, Khan, Asifullah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135540/
https://www.ncbi.nlm.nih.gov/pubmed/37106617
http://dx.doi.org/10.3390/bioengineering10040430
Descripción
Sumario:Lumpy skin disease is a fatal emerging disease of cattle, which has started to gain extensive attention due to its rapid incursions across the globe. The disease epidemic causes economic loss and cattle morbidity. Currently, there are no specific treatments and safe vaccines against the lumpy skin disease virus (LSDV) to halt the spread of the disease. The current study uses genome-scan vaccinomics analyses to prioritize promiscuous vaccine candidate proteins of the LSDV. These proteins were subjected to top-ranked B- and T-cell epitope prediction based on their antigenicity, allergenicity, and toxicity values. The shortlisted epitopes were connected using appropriate linkers and adjuvant sequences to design multi-epitope vaccine constructs. Three vaccine constructs were prioritized based on their immunological and physicochemical properties. The model constructs were back-translated to nucleotide sequences and codons were optimized. The Kozak sequence with a start codon along with MITD, tPA, Goblin 5′, 3′ UTRs, and a poly(A) tail sequences were added to design a stable and highly immunogenic mRNA vaccine. Molecular docking followed by MD simulation analysis predicted significant binding affinity and stability of LSDV-V2 construct within bovine immune receptors and predicted it to be the top-ranked candidate to stimulate the humeral and cellular immunogenic responses. Furthermore, in silico restriction cloning predicted feasible gene expression of the LSDV-V2 construct in a bacterial expression vector. It could prove worthwhile to validate the predicted vaccine models experimentally and clinically against LSDV.