Discovery of vaccine targets and compounds against Malaria transmission

• Grant number: 21/06769-0
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• Start date: February 01, 2022
• End date: January 31, 2028
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Daniel Youssef Bargieri
• Grantee: Daniel Youssef Bargieri
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Anna Caroline Campos Aguiar ; Carolina Horta Andrade ; Fabio Trindade Maranhão Costa ; Maisa da Silva Araújo ; Roberto Rudge de Moraes Barros
• Associated research grant: 13/13119-6 - Cell biology and molecular genetics of hemoparasites, AP.JP
• Associated scholarship(s): 24/17121-0 - Characterization of the CSS protein as a vaccine target in Plasmodium sporozoites, BP.PD; 23/00431-3 - Characterization of the protein encoded by the PBANKA_1459100 gene as a gametogenesis activation receptor in Plasmodium, BP.DD

Abstract

Malaria drug discovery and vaccine development is traditionally focused on studies using asexual blood stages maintained in laboratory cultures. The biology of the sexual stages (gametocytes and gametes) is very different from that of the asexual stages, and few drugs currently in use to treat Malaria are capable of killing the gametocytes, preventing parasite transmission from humans to mosquitoes. Moreover, not many vaccine targets are known for Transmission Blocking (TB) vaccine development. Our lab has developed a high throughput system to screen TB compounds, as well as to search for genes playing a role in transmission and to study their mechanism of action in this process. We have identified new genes that are essential for transmission and one promising compound that blocks transmission in low concentrations. We propose in this project to characterize genes as potential TB targets, as well as a new compound as a TB drug candidate. We will also continue to screen compound libraries to identify new TB compounds to be used in a novel approach aiming at "mosquito treatment". (AU)

Scientific publications

(7)

(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)

FERREIRA, LETICIA TIBURCIO; CASSIANO, GUSTAVO CAPATTI; ALVAREZ, LUIS CARLOS SALAZAR; OKOMBO, JOHN; CALIT, JULIANA; FONTINHA, DIANA; GIL-ITURBE, EVA; COYLE, RACHAEL; ANDRADE, CAROLINA HORTA; SUNNERHAGEN, PER; et al. A novel 4-aminoquinoline chemotype with multistage antimalarial activity and lack of cross-resistance with PfCRT and PfMDR1 mutants. PLOS PATHOGENS, v. 20, n. 10, p. 25-pg., 2024-10-01. (18/24878-9, 19/02171-3, 21/06769-0, 21/13809-9, 17/18611-7)

GAITAN, XIOMARA ALEXANDRA; CALIT, JULIANA; DOBRESCU, IRINA; RAMOS, MARISE SOLORZANO; GIMENEZ, ALBA MARINA; BARGIERI, DANIEL YOUSSEF. Characterisation of the merozoite thrombospondin related anonymous protein (MTRAP) of Plasmodium berghei as a transmission-blocking antigen. Memórias do Instituto Oswaldo Cruz, v. 119, p. 7-pg., 2024-01-01. (18/24878-9, 19/21507-2, 21/06769-0, 14/23083-1, 13/13119-6)

MARQUES, RODOLFO FERREIRA; ABRAHAM, EDIT; MURAMATSU, HIROMI; BARGIERI, DANIEL YOUSSEF; PARDI, NORBERT; LIPINSZKI, ZOLTAN. Expression and purification of E140 protein antigen fragments of Plasmodium vivax and Plasmodium berghei for serological assays. FEBS OPEN BIO, v. N/A, p. 9-pg., 2025-01-15. (22/15895-2, 21/06769-0)

CALIT, JULIANA; PRAJAPATI, SURENDRA K.; BENAVENTE, ERNEST D.; ARAUJO, JESSICA E.; DENG, BINGBING; MIURA, KAZUTOYO; ANNUNCIATO, YASMIN; MOURA, IGOR M. R.; USUI, MIHO; MEDEIROS, JANSEN F.; et al. Pyrimidine Azepine Targets the Plasmodium bc₁ Complex and Displays Multistage Antimalarial Activity. JACS AU, v. 4, n. 10, p. 11-pg., 2024-10-07. (18/24878-9, 21/06769-0, 19/19708-0, 23/02543-3)

XIOMARA ALEXANDRA GAITÁN; JULIANA CALIT; IRINA DOBRESCU; MARISÉ SOLÓRZANO RAMOS; ALBA MARINA GIMENEZ; DANIEL YOUSSEF BARGIERI. Characterisation of the merozoite thrombospondin related anonymous protein (MTRAP) of Plasmodium berghei as a transmission-blocking antigen. Memórias do Instituto Oswaldo Cruz, v. 119, 2024-03-22. (19/21507-2, 13/13119-6, 21/06769-0, 18/24878-9, 14/23083-1)

BORBA, JOYCE V. B.; DE AZEVEDO, BEATRIZ ROSA; FERREIRA, LARISSA A.; RIMOLDI, ALINE; ALVAREZ, LUIS C. SALAZAR; CALIT, JULIANA; BARGIERI, DANIEL Y.; COSTA, FABIO T. M.; ANDRADE, CAROLINA HORTA. Transcriptomics-Guided In Silico Drug Repurposing: Identifying New Candidates with Dual-Stage Antiplasmodial Activity. ACS OMEGA, v. 8, n. 37, p. 7-pg., 2023-09-05. (18/24878-9, 19/21854-4, 21/06769-0, 17/18611-7)

CALIT, JULIANA; ARAUJO, JESSICA E.; DENG, BINGBING; MIURA, KAZUTOYO; GAITAN, XIOMARA A.; ARAUJO, MAISA DA SILVA; MEDEIROS, JANSEN F.; LONG, CAROLE A.; SIMEONOV, ANTON; EASTMAN, RICHARD T.; et al. Novel Transmission-Blocking Antimalarials Identified by High-Throughput Screening of Plasmodium berghei Ookluc. Antimicrobial Agents and Chemotherapy, v. 67, n. 4, p. 11-pg., 2023-03-01. (18/24878-9, 13/13119-6, 21/06769-0, 19/21507-2)