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Vaccine potential of recombinant Oropouche virus lacking the non-structural proteins NSm and NSs (OROV delta_NSm/delta_NSs): evaluation of immunogenicity and protective effect against challenge in a murine experimental model

Grant number: 20/16424-8
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2021
Effective date (End): March 31, 2022
Field of knowledge:Biological Sciences - Microbiology
Principal researcher:Eurico de Arruda Neto
Grantee:Mateus de Vita Mendes Cruz
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The Oropouche virus (OROV), classified in the family Peribunyaviridae, order Bunyavirales and genus Orthobunyavirus, is one of the most frequent emerging arboviruses in Brazil. OROV was first documented in Brazil in 1960 and since then there have been more than 500 thousand cases and 30 outbreaks registered in the legal Amazon. Since the 2000s it has expanded to other regions besides the North Region, with cases in the Southeast, Midwest and Northeast. In addition, the disease caused by the virus - Oropouche fever - has clinical similarities with other seasonal arboviruses, making its etiological diagnosis and differentiation difficult in cases of Dengue, Zika, or Chikungunya, for example. This reveals an underestimation of the number of infections and a high emerging potential for the virus to cause future epidemics. OROV is a negative polarity RNA virus composed of a segmented genome (S, M and L) that encodes structural and non-structural proteins (NSs and NSm). Published studies on viruses from the same family, and even from the same serogroup - such as the Schamllenberg virus (SBV) - have demonstrated the efficacy and safety of mutant viruses deleted for non-structural proteins as a vaccine candidate. In different animal models, viruses DNSm/DNSs triggered a protective and immunogenic effect, without causing disease. In addition, preliminary data from our laboratory in a murine model demonstrated that there is a great reduction in the lethality of animals inoculated with the OROV DNSm/DNSs virus when compared to those inoculated with rOROV WT. Therefore, we propose to evaluate the potential use of recombinant OROV without non-structural proteins OROV DNSm/DNSs as a vaccine candidate to prevent experimental infection in a murine model. We will assess the immunogenic potential by producing neutralizing antibodies, and the ability to protect against challenge with the wild virus. Thus, we seek to contribute to the understanding of the biological bases of NSm and NSs as a potential target to develop alternatives to prevent disease caused by the Oropouche virus.