1- Ph.D. Student, Department of Biology, Faculty of Basic Science, Imam Hossein University, Tehran, Iran 2- Ph.D. Student, Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 3- Ph.D., Department of Microbiology. Karaj Branch, Islamic Azad University, Karaj, Iran 4- Ph.D., Nanotechnology Research Center, Research Institute for Pharmaceutical Sciences and Health Technologies, Baqiyatallah University of Medical Sciences, Tehran, Iran 5- Professor, Applied Virology Research Center, Research Institute for Biomedical Technologies, Baqiyatallah University of Medical Sciences, Tehran, Iran , jafar.salimian@gmail.com
Abstract: (852 Views)
Background and Aim:Several Ebola outbreaks have been recorded worldwide, with most occurring in Central Africa. Given the 50-90% mortality rate among infected individuals and the lack of a specific treatment, there is an urgent need for an effective vaccine to control this disease. In this study, we focus on designing an mRNA vaccine, conducting bioinformatics analyses, predicting structural features, and evaluating the immunological response of a chimeric protein. Materials and Methods: The Ebola virus genome encodes various proteins. Given the functional and protective roles of the glycoprotein (GP) and nucleoprotein (NP), they were used to design a chimeric immunogen, whereas other studies have primarily focused on GP alone. In this study, the conservation of protein and nucleotide sequences was evaluated across different species. Additionally, the allergenicity, antigenicity, toxicity, and physicochemical properties of a recombinant fusion protein resulting from the fusion of these two proteins were analyzed using bioinformatics, and its secondary structure was predicted. Linear and conformational epitopes for B cells, MHC-I, MHC-II, and TCD4 cells were identified using immunoinformatics approaches, and the immune response in a mammalian host was simulated. An mRNA vaccine construct corresponding to the Recombinant Fusion protein was designed, its secondary structure was analyzed, and its sequence was optimized. Results:The designed recombinant fusion protein is an immunogenic molecule with suitable physicochemical properties and secondary structure and exhibits no allergenicity or toxicity. With its multiple epitopes, it can effectively stimulate both humoral and cellular immune responses in the host for at least one month. The designed mRNA vaccine is stable, has a high transcription rate, and, due to the inclusion of the NP protein alongside GP, can be used against various viral strains. Conclusion:Considering the capabilities and advantages of fourth-generation vaccines, the designed mRNA chimera vaccine could be a promising candidate for laboratory studies targeting the Ebola virus.