Designing a multi-epitope subunit vaccine against Orf virus using molecular docking and molecular dynamics.

Autor: Pang F; Department of Veterinary Medicine, College of Animal Science, Guizhou University, Guiyang, China., Long Q; Department of Veterinary Medicine, College of Animal Science, Guizhou University, Guiyang, China., Liang S; Department of Veterinary Medicine, College of Animal Science, Guizhou University, Guiyang, China.
Jazyk: angličtina
Zdroj: Virulence [Virulence] 2024 Dec; Vol. 15 (1), pp. 2398171. Date of Electronic Publication: 2024 Sep 11.
DOI: 10.1080/21505594.2024.2398171
Abstrakt: Orf virus (ORFV) is an acute contact, epitheliotropic, zoonotic, and double-stranded DNA virus that causes significant economic losses in the livestock industry. The objective of this study is to design an immunoinformatics-based multi-epitope subunit vaccine against ORFV. Various immunodominant cytotoxic T lymphocytes (CTL), helper T lymphocytes (HTL), and B-cell epitopes from the B2L, F1L, and 080 protein of ORFV were selected and linked by short connectors to construct a multi-epitope subunit vaccine. Immunogenicity was enhanced by adding an adjuvant β-defensin to the N-terminal of the vaccine using the EAAAK linker. The vaccine exhibited a significant degree of antigenicity and solubility, without allergenicity or toxicity. The 3D formation of the vaccine was subsequently anticipated, improved, and verified. The optimized model exhibited a lower Z-score of -4.33, indicating higher quality. Molecular docking results demonstrated that the vaccine strongly binds to TLR2 and TLR4. Molecular dynamics results indicated that the docked vaccine-TLR complexes were stable. Immune simulation analyses further confirmed that the vaccine can induce a marked increase in IgG and IgM antibody titers, and elevated levels of IFN-γ and IL-2. Finally, the optimized DNA sequence of the vaccine was cloned into the vector pET28a (+) for high expression in the E.coli expression system. Overall, the designed multi-epitope subunit vaccine is highly stable and can induce robust humoral and cellular immunity, making it a promising vaccine candidate against ORFV.
Databáze: MEDLINE