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Immune-mediated mayaro virus protection from wild-type chikungunya virus infection

Grant number: 19/27803-2
Support type:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): February 01, 2021
Effective date (End): January 31, 2022
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Edison Luiz Durigon
Grantee:Rafael Rahal Guaragna Machado
Supervisor abroad: Scott C. Weaver
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : University of Texas Medical Branch at Galveston (UTMB), United States  
Associated to the scholarship:17/24769-2 - Zika virus in postpartum women and newborns: seroepidemiology and molecular characterization, BP.DD

Abstract

Mayaro virus (MAYV) of the genus Alphavirus is a mosquito-transmitted emerging virus that causes an acute febrile illness similar to that produced by chikungunya virus (CHIKV), an evolutionary relative in the Semliki Forest virus complex of alphaviruses. MAYV emergence is typically sporadic, but recent isolations and outbreaks, and an increase in its known distribution, indicate that the virus remains a public health concern. Accompanying these reports is evidence that new vectors, including Aedes spp. mosquitos, recently implicated in the global spread of Zika and CHIKV, are competent for MAYV transmission, which, if true, could facilitate the spread of MAYV beyond its current range. Despite its status as an emerging virus, there are no licensed vaccines to prevent MAYV infection nor therapeutics to treat it. Given the close phylogenetic and antigenic relationship between CHIKV and MAYV, the widespread distribution of CHIKV, and resultant high levels of CHIKV herd immunity throughout the MAYV's distribution, we hypothesize that prior CHIKV immunity may affect MAYV pathogenesis and/or influence its emergence potential. The main objective of this project is to test this hypothesis by investigating the long-term MAYV cross-protection against disease and viremia generated by wild-type CHIKV infection in mice, analyzing the immunology profile of this response. Additionally, we aim to study the potential application of two CHIKV vaccines candidates that may become licensed in the coming years, based on measles-vectored and virus-like particles (VLPs), to control MAYV disease and reduce the potential emergence of this pathogen by limiting human viremia. (AU)