Rational design of novel peptide-based vaccine against the emerging OZ virus

Oz virus (OZV) belongs to the Orthomyxoviridae family which includes viruses with a negative-sense, single-stranded, and segmented RNA genome. OZV is a zoonotic pathogen, particularly since the virus can cause deadly illness when injected intracerebrally into nursing mice. OZV is an emerging pathogen with the potential to spark a pandemic as there is no preventive and licensed treatment against this virus. The goal of this study was to develop a novel multi-epitope vaccination against OZV proteins utilizing immunoinformatics and immunological simulation analysis. This work evaluated immunological epitopes (B cells, MHC-I, and MHC-II) to identify highly antigenic OZV target proteins. Shortlisted epitopes were joined together by using appropriate linkers and adjuvants to design multi-epitope vaccine constructs (MEVC). The vaccine models were designed, improved, validated, and the globular regions and post-translational modifications (PTMs) were also evaluated in the vaccine's structure. Molecular docking analysis with the Toll-like receptor (TLR4) showed strong interactions and appropriate binding energies. Molecular dynamics (MD) simulation confirmed stable interactions between the vaccines and TLR4. Bioinformatics tools helped optimize codons, resulting in successful cloning into appropriate host vectors. This study showed that the developed vaccines are stable and non-allergenic in the human body and successfully stimulated immunological responses against OZV. Finally, a mechanism of action for the designed vaccine construct was also proposed. Further experimental validations of the designed vaccine construct will pave the way to create a potentially effective vaccine against this emerging pathogen.