Development of a Multi-Epitope Subunit Vaccine Against a Neglected Arbovirus of the Americas: an Immunoinformatics and Molecular Modeling Approach.
The Mayaro virus (MAYV) is an emerging arbovirus in the Americas that can cause debilitating arthritogenic diseases. Although the biology of MAYV is not fully understood, it is known to be closely related to arthritogenic alphaviruses such as chikungunya, Ross River, and O’nyong nyong viruses. Effective control of the spread of these diseases requires identification of infected individuals and the development of preventive and prophylactic therapies. However, currently, the only available approach for controlling MAYV is vector control, as there are no licensed vaccines to prevent MAYV infection or therapies to treat it. In this study, we used immunoinformatics and molecular modeling approaches to identify potential T cell epitopes for vaccination against the Mayaro virus. To do this, we analyzed 127 MAYV genomes sequenced in the Americas (08 Bolivia, 72 Brazil, 04 French Guiana, 05 Haiti, 20 Peru, 04 Trinidad and Tobago, and 14 Venezuela) and identified short protein sequences that can bind to MHC class I and class II alleles. These promiscuous epitopes were selected based on their conservation and immunogenicity. Through immunoinformatics and molecular modeling analyses, we identified 56 potential MHCI/TCD8+ and 29 potential MHC-II/TCD4+ epitopes, with only specific protein sequences (nsP1191-199, nsP1501-509, nsP1498-506, nsP3348-356, nsP4305-314 and nsP4212-221(nsP157-71 , nsP116-30, nsP1182-196, nsP1180-194, nsP115-29, nsP2640-654, nsP2639-653, nsP2679-693, nsP2677-691 , nsP2680-694, nsP3127-141, nsP362-76, nsP4414-428, nsP4413-427, nsP4412-426 and nsP4372-386) TCD8+ (TCD4+) exhibiting high antigenicity, conservation, non-allergenicity, non-toxicity, and excellent population coverage. Based on these results, we developed a multiepitope vaccine coupled to the TLR3 receptor and improved its quality through quantum mechanical calculations. These results have important implications for advancing diagnosis, vaccine development, and immunotherapeutic interventions against the Mayaro virus.