Study of the therapeutic potential of peptides generated by Galleria mellonella using the epitope masking technique

• Grant number: 23/03240-4
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2024
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Andrei Moroz
• Grantee: Andrei Moroz
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Ana Marisa Fusco Almeida ; Maria José Soares Mendes Giannini
• Associated scholarship(s): 24/23402-1 - Therapeutic Platforms for Paracoccidioidomycosis, BP.PD; 24/23484-8 - Production and characterization of anti-Cryptococcus neoformans monoclonal Antibodies using the multiple tolerization subtractive immunization protocol (MTSI) and epitope masking, BP.DD; 23/17852-1 - Application of the epitope masking technique using G. mellonella as a model in C. neoformans infection., BP.TT

Abstract

Course studies of human pathologies are important for understandingmechanisms, identification of therapeutic targets and possible treatments. Considering thecurrently developed research, one of the problems presented refers to theanimals to be used, since this theme has many scientific ramificationsand ethical. Therefore, the use of alternative animals appears as an alternative for studiesin vivo due to its complexity and because it has metabolic pathways capable of elucidating topicsrelated to the study of diseases. One of them, Galleria mellonella, is an insect belonging toto the Lepidoptera, also known as the honey moth. It has its larval stage that awakensmuch interest in science due to its high range of investigative possibilities, such as theimmune response generated by hemocytes and peptides, described by some authors as ahumorous response. Another strand of research is its use for host fungal interaction studies, in some of these studies, the model demonstrated that during the infection ofCryptococcus neoformans it was possible to delineate results that elucidated the course ofpathogenesis in the insect, relating fungal virulence factors and innate immune response. Allyto this, in the search for methods that can contribute to the discovery of new biomarkerstumors, or even new therapeutic targets, the antigen masking technique hasproved to be attractive, as it modulates the immune system, while directing the generation ofantibodies/peptides against rare, low-expressing epitopes that may play a rolerelevant in the establishment of diseases. Therefore, this project proposes the use of aepitope masking technique to limit the array of antigens exposed to theimmune system of Galleria mellonella to evaluate its immune response regarding the production ofantimicrobial peptides, and compare the plasticity of this immune response in relation tocontrols (non-masked). Among the analyzes that will elucidate these doubts are theisolation and purification of peptides by chromatography, and the biological characterization ofagainst the microorganism used as an immunizer, aiming to identify activitymicrobial. Furthermore, sequencing will be carried out by mass spectrometry toidentify the composition of amino acids present in these peptides. (AU)