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 Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2019
• End date: March 31, 2020
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Irene da Silva Soares
• Grantee: Tarsila Mendes de Camargo Oliva
• Host 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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LIMA, LUCIANA C.; MARQUES, RODOLFO F.; GIMENEZ, ALBA MARINA; FRANCOSO, KATIA S.; ALIPRANDINI, EDUARDO; CAMARGO, TARSILA M.; AGUIAR, ANNA CAROLINE C.; PEREIRA, DHELIO B.; RENIA, LAURENT; AMINO, ROGERIO; et al. A Multistage Formulation Based on Full-Length CSP and AMA-1 Ectodomain ofPlasmodium vivaxInduces High Antibody Titers and T-cells and Partially Protects Mice Challenged with a TransgenicPlasmodium bergheiParasite. MICROORGANISMS, v. 8, n. 6, JUN 2020. (12/13032-5, 14/18102-7, 18/17364-9)

DOBRESCU, IRINA; DE CAMARGO, TARSILA MENDES; GIMENEZ, ALBA MARINA; MURILLO, OSCAR; AMORIM, KELLY NAZARE DA SILVA; MARINHO, CLAUDIO ROMERO FARIAS; SOARES, IRENE SILVA; BOSCARDIN, SILVIA BEATRIZ; BARGIERI, DANIEL YOUSSEF. Protective Immunity in Mice Immunized With P. vivax MSP1(19)-Based Formulations and Challenged With P. berghei Expressing PvMSP1(19). FRONTIERS IN IMMUNOLOGY, v. 11, FEB 19 2020. (13/13119-6, 14/50631-0, 12/13032-5, 14/23083-1, 18/17364-9, 18/20468-0)