Desenvolvimento de uma vacina de subunidade multi-epítopo contra um arbovírus negligenciado das Américas: uma abordagem por imunoinformática e modelagem molecular

Abstract

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 MHC-I/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 for CD8+ T cells and 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 for CD4+ T cells) 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. Based on the results obtained, the identification of potential T-cell epitopes may be important for understanding the pathogenesis and immune response to this infection. Additionally, the development of vaccines and immunotherapeutic interventions against Mayaro virus may have significant implications for future research in this area as well as for effective control of the dissemination of emerging arboviral diseases. This can help prevent outbreaks and epidemics, reducing the impact of these diseases on the population and contributing to public health advancement.