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Evaluation of the immunogenicity of novel multi-stage recombinant proteins candidates for the development of a vaccine to Plasmodium vivax

Grant number: 18/17364-9
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2019
Effective date (End): March 31, 2021
Field of knowledge:Biological Sciences - Parasitology
Principal Investigator:Irene da Silva Soares
Grantee:Tarsila Mendes de Camargo Oliva
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:12/13032-5 - Generation and analysis of the immunogenicity of recombinant proteins based on the different allelic forms of the circumsporozoite antigen of Plasmodium vivax aiming at the development of a universal vaccine against malaria, AP.TEM

Abstract

The search for an effective vaccine against malaria caused by Plasmodium vivax is one of the main goals of global research and will likely require a product that includes several antigens from the parasite cycle. To achieve this goal, we propose to develop a multi-antigen and multi-stage vaccine capable of preventing infection and / or clinical manifestations of malaria vivax. Thus, we propose to fuse pre-erythrocyte phase Circumsporozoite protein (CSP) with blood phase antigens: the merozoite apical membrane protein AMA1 (PvCSPCT-AMA1), the 19 kDa portion of the merozoite MSP1 surface protein (PvCSPCT- MSP119) and the Duffy Binding Protein DPB-RII protein (PvCSPCT-DBP-RII). Group work and literature demonstrate that these antigens are promising and capable of generating protective antibodies. For this the recombinant proteins will be expressed in Pichia pastoris following protocol already established by the group. Purification and characterization will be done by high performance chromatography, followed by immunoblotting and immunofluorescence assays using slides with fixed parasites (sporozoites and merozoites). C57BL / 6 mice will be immunized with the proteins described in the presence of the Poly (I: C) adjuvant. The humoral response will be measured by ELISA and the cellular response by TCD4 + and TCD8 + and ELISPOT proliferation assays. The protective efficacy of these antibodies will be performed using transgenic parasites of P. berghei rodents expressing the CS protein of P. vivax (Pb-Pv). We hope with this study to obtain an effective multi-antigen and multi-stage vaccine and to advance to clinical trials.

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