Heterologous expression of external portions of transmembrane ¿-barrel proteins from Leptospira interrogans for the development of new vaccine formulations against leptospirosis

• Grant number: 24/17775-0
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: January 06, 2025
• End date: February 15, 2025
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Odir Antônio Dellagostin
• Grantee: Marina Raspante de Oliveira Ferreira
• Host Institution: Centro de Desenvolvimento Tecnológico (CDTec). Universidade Federal de Pelotas (UFPEL). Pelotas , SP, Brazil

Abstract

The proposal aims to develop new vaccine formulations against leptospirosis, a widely distributed and underreported zoonosis, especially in tropical regions and developing countries. The disease affects about 103 million people annually, causing approximately 58,900 deaths. Leptospirosis is primarily transmitted through contact with the urine of infected animals, such as rodents, dogs, cattle, and pigs, and can be effectively controlled through vaccination. Currently, the available vaccines against leptospirosis are bacterins, composed of inactivated Leptospira cells. However, these vaccines offer short-term protection and are limited to certain serovars, in addition to potentially causing undesirable side effects, such as fever and nausea, limiting their use in humans. Given this, there is an urgent need to develop more effective vaccines that provide broader protection. Vaccines based on recombinant DNA technology emerge as a promising alternative, offering greater safety and the possibility of protecting against multiple serovars. The proposal in question aims to heterologously express two chimeras based on outer membrane proteins (OMPs) OmpL72 and OmpL94, identified as potential antigens for the development of more efficient vaccines. These proteins belong to the group of ¿-OMPs, which play a crucial role in transporting essential nutrients, such as iron and vitamin B12, into the bacterial cell during infection. Immunization against these proteins can enhance opsonization, promoting phagocytosis and bacterial lysis, as well as blocking the dissemination of the bacteria. The project will use Reverse and Structural Vaccinology techniques to standardize the expression of these proteins in Escherichia coli, purify them, and incorporate them into a recombinant subunit vaccine. Additionally, the antigenicity of the vaccine formulations will be characterized to ensure their effectiveness. It is expected that these vaccines will be able to induce effective cross-immunity, protecting against multiple pathogenic species of Leptospira. The expected impacts include a significant contribution to the control of leptospirosis, a disease neglected by public health authorities. If successful, the new vaccines will have the potential to overcome the limitations of current vaccines and protect a broader population. Additionally, the project will provide training and education for undergraduate and graduate students, strengthening research in this area.