Functional characterization of antibodies against Plasmodium vivax merozoite surface protein MSP-119

• Grant number: 17/25591-2
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): May 01, 2018
• Effective date (End): June 04, 2019
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Marcelo Urbano Ferreira
• Grantee: Marcela Maria Santiago Timossi
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/18740-9 - Scientific bases for residual malaria elimination in the Brazilian Amazon, AP.TEM

Abstract

Approximately 212 million malaria cases and more than 400,000 deaths are registered annually in the world. In Brazil, 143,000 malaria cases were recorded in 2014, 88% of which were due to Plasmodium vivax. Merozoites are stages of the parasite responsible for the invasion and destruction of red blood cells, causing clinical symptoms of malaria.They are covered by several merozoite surface proteins (MSPs); the most abundant amongst them is the merozoite surface protein 1 (MSP-1), a major target for the development of vaccines against the parasite's blood stages. MSP-1 is synthesized as a 19 5kDa precursor, which undergeso two steps of enzymatic cleavage; only the 19-kDa C-terminal fragment, known as MSP-119, remains anchored to the surface of merozoites, using band 3 as a receptor during adhesion and invasion of erythrocytes. Antibodies against P. falciparum MSP-119 (PfMSP-119), either naturally acquired or induced by experimental immunization, are capable of inhibiting red blood cell invasion in vitro. Nevertheless, it is unknown whether antibodies against PvMSP-119, the homologous protein of P. vivax, are able to block invasion. This significant knowledge gap is due in part to the difficulties of maintaining P. vivax in culture in vitro. To fill this gap, our laboratory has been optimizing ex-vivo assays to characterize the ability of antibodies against various P. vivax antigens to inhibit the invasion of red blood cells while using newly patient-derived or cryopreserved parasites. This master's project aims to optimize several steps of our ex-vivo test protocols to evaluate whether antibodies against PvMSP-119, either acquired by individuals naturally exposed to malaria in the Brazilian Amazon or induced in mice by plasmid immunization, are able to block red blood cell invasion by P. vivax merozoites ex-vivo. (AU)