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Application of liposomes for RNA vaccines against the Plasmodium falciparum PfHR5 antigen and establishment of a technical approach for guided liposomes

Grant number: 16/19145-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2017
Effective date (End): June 30, 2020
Field of knowledge:Interdisciplinary Subjects
Principal Investigator:Gerhard Wunderlich
Grantee:Wesley Luzetti Fotoran
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

An alternative to the use of inactivated or attenuated whole organisms or recombinant proteins as vaccines is the use of plasmid DNAs which encode the desired vaccine antigen. Genetic vaccines and delivery of drugs to specific tissues have two great challenges: 1-Delivery of sufficient quantities of RNA or DNA to develop immune responses against specific vaccine targets and side effects produced by RNA/DNA inoculation; 2- Physiologic barriers, such as the blood-brain barrier and specific ligands for transfer of therapeutic molecules to the target tissue. Biotechnological approaches to overcome these points are: 1-Use of RNA replicons instead of classic plasmid DNA vaccines, 2- Use of liposomes in nanoscale to stabilize the cargo until the arrival at the correct site of action, enhancing delivery, 3- Antibody or ligand-guided liposomes to reach specific tissues and to bypass barriers such as the blood-brain barrier. Herein, we propose the use of cationic liposomes with RNA replicon cargo in order to produce humoral immune responses against PfRH5, the most promising vaccine candidate against P. falciparum to date. Additional to the use of cationic liposomes, we propose the employment of liposomes loaded with therapeutic agents to target hardly accessible tissues, such as the nervous tissue. The use of RNA replicons is a novel application and has not yet been applied in Brazil. The connection of each approach probably opens up new avenues for the treatment of a number of diseases.