Immunoinformatic based Development of a Multi-Epitope Precision Vaccine Targeting Glycoprotein and RdRp of Oropouche...

To design high immunogenic vaccine against the Oropouche virus (OROV). The OROV is a neglected arbovirus endemic to Central and South America, causes oropouche fever, which can progress to severe complications such as meningitis and hemorrhagic symptoms.

We utilized immunoinformatic and molecular dynamic simulation approaches to design highly immunogenic vaccines against OROV. This observational study, carried out between January and August 2024 in Saudi Arabia. As it involves an in-silico method, ethical consent was not required.

Docking analysis confirmed the stable interaction of the designed vaccines with human toll-like receptors (TLR)-3, producing binding scores of -300.78, -306.19, and -288.60 kcal/mol for the glycoprotein, ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), and combined vaccine, respectively. Furthermore, molecular dynamics simulations supported the stability of the vaccine-TLR-3 complexes. The calculated total binding free energies were -107.44 kcal/mol for glycoprotein-TLR-3, -33.64 kcal/mol for RdRp -TLR-3, and -78.62 kcal/mol for the combined vaccine-TLR-3 interaction. The computed codon adaptation index (CAI) values for the vaccines were notably 0.96, with guanine-cytosine (GC) content ranging between 65% and 66%, suggesting strong potential for high expression in the pET28a+ vector. The analysis of immune simulation showed rapid antigen clearance, accompanied by sustained and elevated immunoglobulin (Ig)M and IgG responses.

This study presents a potent and secure vaccine candidate to combat the emerging Oropouche virus infection, which requires further experimental validation.