Development of lipid nanoparticles (LNPs) containing mRNA immunogenic domains of LigA and LigB of Leptospira interrogans and evaluation in animal model

• Grant number: 25/02883-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2025
• End date: January 31, 2029
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Ana Lucia Tabet Oller do Nascimento
• Grantee: Henrique Machado Pires
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 19/17488-2 - Advancing the understanding of pathogenesis and virulence of Leptospira interrogans through proteomics, structural, mutagenesis and immunological analyses, AP.TEM

Abstract

Leptospirosis is a zoonosis of global importance that in the last ten years has been considered one of the main emerging infectious diseases. It is caused by a group of pathogenic bacteria of the genus Leptospira. Man is the accidental and terminal host, presenting different clinical manifestations. The disease affects around 1 million people annually, resulting in around 60,000 deaths, and only the indicated vaccines are available for prophylaxis. mRNA vaccines for infectious bacterial diseases are scarce, with only one evidenced in the literature, which is for prophylaxis of Yersinia pestis, which causes bubonic plague. Thus, the mRNA of immunogenic L. interrogans protein domains, as well as their epitopes, encapsulated in lipid nanoparticles (PNLs) emerge as vaccine candidates against leptospirosis. Thus, the aim of the work is to obtain immunogenic epitopes as well as the corresponding LigA and LigB mRNA, the expression and purification of these domains and their encapsulation in PNLs for the evaluation of immunogenicity. Protein epitopes and mRNA will be obtained encapsulated in liposomes (LPs). mRNA transfection in animal cells will be evaluated both by western blotting and flow cytometry. mRNA and epitope immunogenicity studies will be carried out in BALB/c mice, as well as cell-mediated immune responses and cytokine profiles using ELISA. The immunoprotection activity will be evaluated in hamsters after inoculation with mRNA-LP and subsequent challenge with a virulent strain of L. interrogans serovar Kennewicki isolated from Pomona Fromm. The acquisition and immunological validation of both mRNAs and epitopes of the immunogenic domains of LigA and LigB encapsulated in liposomes contribute to the development of an innovative vaccine for the prophylaxis of leptospirosis. (AU)