Last Updated: 15/10/2025

RNA as a new vaccine strategy for the control of Chagas disease, leishmaniasis and malaria

Objectives

This research grant proposes the development of RNA vaccines to combat Chagas disease, leishmaniasis, and malaria, leveraging the rapid production and strong immune response capabilities demonstrated during the COVID-19 pandemic. The project involves synthesizing RNA with specific coding sequences and optimizing lipid nanoparticle formulations for effective delivery in animal models, building on existing collaborations and research in parasitic protozoa.

Principal Investigators / Focal Persons

Santuza Maria Ribeiro Teixeira

Rationale and Abstract

Different vaccine strategies have been used by research groups in Brazil and abroad to control diseases caused by Trypanosoma cruzi, Leishmania infantum, and Plasmodium vivax. However, despite great efforts, no vaccine developed in Brazil has reached clinical trials. As demonstrated in the COVID-19 pandemic, RNA vaccines are a promising alternative to other vaccination approaches due to their rapid production time, cost-effectiveness, versatility in design, and ability to induce strong cellular and humoral immune responses. To test RNA vaccines for three diseases, the study propose to use methodologies for the in vitro synthesis of RNA containing the coding sequence of vaccine antigens and regulatory sequences important for translation and stability of RNA in cells. In addition, to produce RNA capable of generating antigens in cells, modification of the 5′ (CAP) and 3′ (polyA tail) ends will be performed, as well as the incorporation of modified nucleotides. Finally, for inoculation in animal models, the RNA will be encapsulated in lipid nanoparticles (LNPs) containing ionizable cationic lipids that interact with the RNA, protecting it from degradation and favoring delivery into the cell cytoplasm. In addition to in vitro synthesis, the formulation stage is the second biggest challenge for the production of RNA vaccines and requires the optimization of protocols with various lipid mixtures. The research group has been working on research on mRNAs in parasitic protozoa for several years and, in collaboration with groups from Fiocruz and USP, the team have sought to develop vaccines against Chagas disease, leishmaniasis and malaria using recombinant antigens. In partnership with the group from the School of Pharmacy, specialists in lipid formulations, the investigator have begun studies aimed at testing RNA vaccines for these three diseases, the results of which will be compared to those obtained with recombinant antigens.

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