Characterization of the cysteine-rich small secreted (CSS) protein roll in the Plasmodium berghei sporozoite transmission

• Grant number: 22/05918-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): March 01, 2023
• Effective date (End): February 01, 2024
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Daniel Youssef Bargieri
• Grantee: Xiomara Alexandra Gaitán
• Supervisor: Rogerio Amino
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: Institut Pasteur, France
• Associated to the scholarship: 19/21507-2 - Characterization of the cysteine-rich small secreted (CSs) protein as a vaccine candidate against Plasmodium, BP.DR

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. Cysteine-rich Small Secreted (CSS) protein of Plasmodium can be used as a target in vaccine formulations against malaria. The CSS protein was recently described to interact with RIPR in P. knowlesi, and our laboratory has found CSS interacting with RIPR in P. berghei. RIPR is part of protein complex on the membrane of P. falciparum, where it interacts with PfRh5 and PfCyRPA. Antibodies against members of this complex (RIPR-interacting proteins) inhibit parasite invasion into host cells, thus these proteins are all considered vaccine candidates. Since PbCSS interacts with PbRIPR and is essential for parasite survival, we analyzed if antibodies targeting PbCSS could inhibit parasite invasion of erythrocytes. Our results indicate that PbCSS trigger a strong antibodies response in immunized mice; however, they failed to protect challenged mice against infection. Given that PbCSS is highly expressed in sporozoites, this project will evaluate the role of the CSS on the sporozoite transmission and test the usefulness of PbCSS as a pre-erythrocytic antigen. (AU)