mRNA-RVGP- LNP Vaccine Proposal Platform against Rabies.

• Grant number: 24/05287-0
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2024
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Soraia Attie Calil Jorge
• Grantee: Soraia Attie Calil Jorge
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Durvanei Augusto Maria ; Wagner Quintilio
• Associated scholarship(s): 24/20247-5 - Rabic Glycoprotein mRNA in lipidic nanoparticles production., BP.TT

Abstract

Rabies is a zoonosis responsible for approximately 59,000 fatal human cases annually worldwide (WHO, 2024) and causes significant economic losses for both animal and human health. Rabies is one of the few viral diseases that can be prevented through vaccination, both before and after infection. As a zoonosis, the vaccination of domestic or farm animals is considered the best preventive measure against human rabies in at-risk areas.Despite existing vaccines against rabies, an interesting vaccine alternative is the mRNA platform, which has been extensively studied since the Covid-19 pandemy. It is a promising alternative due to the speed of vaccine development, safe administration as mRNA is non-infectious and non-integrating, and high efficacy, with modifications that can be used to enhance mRNA stability. One such modification is the formulation of carrier molecules, such as lipid nanoparticles, which allows for rapid absorption and reduces the chances of mRNA being recognized by the immune system and degraded by endogenous nucleases.Therefore, this work aims to develop an mRNA-LNP platform carrying the rabies antigen (RVGP-Rabies Virus Glycoprotein) recognizable by the immune system in mammalian cells. To achieve this, the plasmid will be constructed in replicative and non-replicative forms, transcribed in vitro into mRNA, and delivered either encapsulated or not in lipid nanoparticles (LNP), for comparative expression and characterization purposes. The mRNA-RVGP obtained in this project can also be used for other delivery systems, such as exosomes, gold particles, or silica particles in collaboration with other groups from Instituto Butantan or USP. (AU)