Identification by Phage Display of peptide ligands for extracellular vesicles (EVs) released by Leishmania amazonensis promastigotes with distinct virulence profiles

• Grant number: 25/14100-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2025
• End date: May 31, 2028
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia Xander Batista
• Grantee: Ester da Silva Duenha
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated research grant: 24/21260-5 - Extracellular vesicles of Leishmania amazonensis: proteomic characterization and protective evaluation in murine models, AP.R

Abstract

Leishmaniasis is a group of infectious diseases with a wide spectrum of clinical manifestations. More than 30 species belonging to the genus Leishmania are the etiological agents of leishmaniasis. Leishmania (Leishmania) amazonensis is one of the etiological agents of the cutaneous form of the disease in Brazil. The initial interaction between the parasite and the mammalian host involves multiple molecules from both the parasite and the host. In recent years, extracellular vesicles (EVs) released by parasites have emerged as key elements in the parasite-host interaction. EVs are lipid bilayer structures that transport proteins, RNAs, and other bioactive components, participating in processes such as immune evasion, and modulation of the inflammatory response. Our group showed that EVs from L. amazonensis were capable of exacerbating infection in murine models when co-injected with parasites. However, prior immunization with EVs induced partial protection in animals subsequently challenged with L. amazonensis. These findings indicated that EVs have potential as therapeutic and vaccine targets. In this context, the present project aims to identify peptides that bind to L. amazonensis EVs using Phage Display technology. The phages selected from the Phage Display libraries will be subjected to binding assays and functional studies with EVs and parasites. In addition, peptides identified from the Phage Display libraries will be synthesized and evaluated for their potential to bind to EVs and block the internalization of EVs and parasites by phagocytic cells in vitro. In vivo assays will be conducted using the peptides to experimentally evaluate the therapeutic potential in BALB/c mice infected with L. amazonensis, assessing parameters such as lesion evolution, parasite load, cytokine profile, and histopathology. Thus, this study aims to identify ligands of L. amazonensis EVs and evaluate their functionality and therapeutic potential in an in vitro and in vivo infection model. The results obtained may contribute to a better understanding of the role of L. amazonensis EVs in host interactions and to exploring their potential as specific molecular targets for leishmaniasis.