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Plasmodium vivax vaccine development and antigen discovery using P. berghei malaria models.

Grant number: 14/23083-1
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2015
Effective date (End): June 30, 2019
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal Investigator:Daniel Youssef Bargieri
Grantee:Irina Dobrescu
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:13/13119-6 - Cell biology and molecular genetics of hemoparasites, AP.JP

Abstract

Malaria is a preventable, diagnosable and treatable disease. Yet, the disease causes thousands of deaths every year, and millions of people are still endangered. Almost all malaria cases worldwide are due to infection with Plasmodium vivax or P. falciparum. There is an urgent need to eliminate malaria, since drug resistance is reappearing, and there seems to be a general agreement that elimination is not simply a matter of intensifying the use of available tools. New strategies, like efficient vaccines, will be required.Developing a malaria vaccine is one of the greatest challenges in biomedical sciences. Vaccine development against P. vivax is even more challenging, because the parasite cannot be continuously cultured in laboratories. The lack of cultures has been an obstacle slowing pre-clinical tests of vaccine formulations against P. vivax based on known antigens, and also makes new antigen discovery particularly difficult.This project has two major proposals: i) use a malaria murine model, P. berghei, to construct hybrid transgenic parasites expressing a P. vivax blood stage antigen, MSP1(19), and use the hybrid P. berghei to challenge mice vaccinated with available PvMSP1 based vaccines, testing the efficacy of these formulations; ii) use P. berghei to search for Plasmodium functional homologs of the P. falciparum-specific invasion molecule PfRh5, a promising vaccine antigen candidate that has recently been shown to bind CD147 on the surface of host cells and to be essential for invasion.The aim of these proposals is to move forward with P. vivax vaccine development by generating a platform to test available formulations, for which tests of efficacy are lacking, and by searching for a putative new Plasmodium invasion pathway, that should guide the search for new P. vivax invasion pathways to serve as vaccine targets.

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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)
CALIT, JULIANA; DOBRESCU, IRINA; GAITAN, XIOMARA A.; BORGES, MIRIAM H.; RAMOS, MARISE S.; EASTMAN, RICHARD T.; BARGIERI, DANIEL Y.. Screening the Pathogen Box for Molecules Active against Plasmodium Sexual Stages Using a New Nanoluciferase-Based Transgenic Line of P-berghei Identifies Transmission-Blocking Compounds. Antimicrobial Agents and Chemotherapy, v. 62, n. 11, . (14/23083-1, 13/13119-6, 16/16649-4)
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, . (13/13119-6, 14/50631-0, 12/13032-5, 14/23083-1, 18/17364-9, 18/20468-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
DOBRESCU, Irina. Plasmodium vivax vaccine development and antigen discovery using P. berghei malaria models.. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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