Characterization of neutralization mechanisms and antibody-mediated effector functions in Oropouche virus infection

• Grant number: 24/12668-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2024
• End date: July 31, 2029
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: José Luiz Proença Módena
• Grantee: Gabriel Caetano Scachetti
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The Oropouche virus (OROV) is a neglected arbovirus endemic to Latin America and the Caribbean, causing Oropouche fever, an exanthematous febrile illness that can progress to neurological conditions. From December 2023 to the present, there has been a substantial increase in the number of cases of Oropouche Fever in Brazil and other South American countries, as well as the geographical expansion to historically non-endemic and highly populated areas in Brazil, such as Bahia, Minas Gerais, Rio de Janeiro, and Santa Catarina. Due to its segmented genome, OROV is susceptible to reassortment events, which occur when two related viruses co-infect a cell, resulting in progeny with mixed genomic segments. This can alter the virus fitness and enable the escape from neutralizing antibodies produced in previous infections. This is crucial because recent studies in murine models indicate a central role of neutralizing antibodies and marginal zone B cells, through IgM production, in controlling neuroinvasion and death caused by OROV. However, little is known about the protective role and duration of the effective humoral response for controlling OROV pathogenesis in humans. Therefore, we aim to characterize the action of neutralizing antibodies, the recognition sites, and the effector functions mediated by antibodies against OROV using systems serology. To this end, serum samples from convalescent patients will be mapped for their ability to recognize the different epitopes of this virus, evaluated for their neutralizing capacity by PRNT50 assays, or analyzed through assays for antibody-dependent complement deposition (ADCD), antibody-dependent cellular phagocytosis (ADCP), antibody-dependent neutrophil phagocytosis (ADNP), and antibody-dependent NK cell activation (ADNK) for their ability to induce antibody-mediated effector functions. Characterizing the mechanisms of neutralization and antibody-mediated effector functions against the Oropouche virus is crucial for developing effective prevention and treatment strategies, helping to control the virus spread and reduce the impact of complications associated with the infection.