PRODUCTION OF AN INFECTIOUS ATTENUATED CLONE OF THE MAYARO VIRUS AND PRECLINICAL ANALYSIS OF ITS POTENTIAL AS A VACCINE IN A SUSCEPTIBLE MICE MODEL CD11ccreIRF5f/f

• Grant number: 24/01894-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2025
• End date: February 28, 2029
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: José Luiz Proença Módena
• Grantee: Bruno Brito Pereira da Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Mayaro (MAYV) is an arthritogenic alphavirus, endemic to the Americas and phylogenetically close to the Chikungunya virus. This virus normally circulates in non-human primates, birds and some species of rodents in the wild, mainly in the Amazon region. However, the destruction of forest areas and the redistribution of vectors as a result of global warming have favored the spread of this virus to new areas of Brazil and other countries. The infection can be asymptomatic or progress to acute febrile illnesses, chronic arthritis or neurological complications and deaths. However, the pathophysiological mechanisms associated with MAYV infection in humans are not yet completely understood and there are no vaccines or antivirals licensed against MAYV. Recently, we demonstrated that animals with deletion of IRF 5 in dendritic cells (CD11ccreIRF5f/f) are partially vulnerable to MAYV infection. Approximately 40% of these mice die and show signs of neurological impairment after five days of infection. In this project we intend to use this animal model to evaluate the vaccine efficacy of attenuated MAYV strains that will be generated using reverse genetics approaches. The attenuated variant of MAYV will be generated by deletions in the coding region of the MAYV non-structural protein nsP3.