Design of chimera vaccine against cutavirus using vaccinomics and immunoinformatics approaches.

[UNLABELLED] Cutavirus (CuV) is a newly discovered human parvovirus, which gained tremendous interest due to its association with cutaneous lymphoma T cells. CuV transmission primarily occur via fecal-oral route and identified as a causal agent of diarrhea. The current study based on prediction of novel multi-epitopic potential vaccine models against CuV by predicted by selecting highly antigenic proteins using reverse vaccinology approaches. A top-ranked T and B cell epitopes from lead vaccine candidate proteins were selected and linked via immunogenic adjuvant peptides and linker sequences to design model vaccine. The models were assessed in terms of physicochemical properties including antigenicity, non-allergenicity, and their binding affinities to TLR4 immune receptors. The in-silico restriction and cloning analysis were pursued to check the expression capacity of model vaccine. Several vaccine models were designed from lead epitopes of CuV vaccine candidates' proteins along with combination of immune-enhancer adjuvants and linkers. Physicochemical and immunoinformatics analyses prioritized a V2 model construct as top-ranked. The molecular docking and molecular dynamic simulation analyses ensured the V2 construct molecular stability and strong interaction with TLR4 immune receptor with binding affinity of - 41.27 kcal/mol. The normal mode analysis (NMA) predicted improved flexibility, proper molecular mobility, and decreased protein deformability of immune complex for the generation of powerful immune response. Molecular dynamics simulation confirmed the structural stability of the V2-TLR4 complex with minimal RMSD fluctuations and sustained hydrogen bonding. Principal component analysis (PCA) revealed limited conformational shifts, indicating a stable dynamic behavior of the vaccine-receptor complex. These results support the robust interaction and stability of the designed vaccine, reinforcing its potential for effective immune activation. Immune simulation predicted a strong primary and memory immune response with elevated levels of IgG, IFN-γ, and T-cell activity. Codon optimization yielded a CAI score of 0.98 and GC content of 53.1%, indicating efficient expression in . The multi-epitope vaccine construct prioritized in the current study is effectively bind with immune receptors and elicit potent immune response against CuV.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s40203-025-00467-6.