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 Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2017
• End date: August 31, 2020
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Gerhard Wunderlich
• Grantee: Wesley Luzetti Fotoran
• Host 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.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CUBILLOS, ELIANA F. G.; PRATA, ISADORA OLIVEIRA; FOTORAN, WESLEY LUZETTI; RANFORD-CARTWRIGHT, LISA; WUNDERLICH, GERHARD. The Transcription Factor PfAP2-O Influences Virulence Gene Transcription and Sexual Development in Plasmodium falciparum. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, JUN 28 2021. (16/12659-5, 17/24267-7, 15/17174-7, 16/19145-7)

VENCESLAU-CARVALHO, ALEXIA ADRIANNE; FAVARO, MARIANNA TEIXEIRA DE PINHO; PEREIRA, LENNON RAMOS; RODRIGUES-JESUS, MONICA JOSIANE; PEREIRA, SAMUEL SANTOS; ANDREATA-SANTOS, ROBERT; ALVES, RUBENS PRINCE DOS SANTOS; CASTRO-AMARANTE, MARIA FERNANDA; RODRIGUES, KARINE BITENCOURT; DA SILVA, JAMILE RAMOS; et al. Nano-multilamellar lipid vesicles loaded with a recombinant form of the chikungunya virus E2 protein improve the induction of virus-neutralizing antibodies. Nanomedicine-Nanotechnology Biology and Medicine, v. 37, OCT 2021. (17/23281-6, 16/19145-7, 16/08204-2, 17/24769-2, 16/20045-7, 16/23560-0)

FOTORAN, WESLEY L.; DA SILVA, JAMILE RAMOS; GLITZ, CHRISTIANE; FERREIRA, LUIS CARLOS DE SOUZA; WUNDERLICH, GERHARD. Establishment of an Antiplasmodial Vaccine Based on PfRH5-Encoding RNA Replicons Stabilized by Cationic Liposomes. PHARMACEUTICS, v. 15, n. 4, p. 17-pg., 2023-04-01. (17/24267-7, 21/13727-2, 16/20045-7, 16/19145-7)

FOTORAN, WESLEY L.; MUENTEFERING, THOMAS; KLEIBER, NICOLE; MIRANDA, BEATRIZ N. M.; LIEBAU, EVA; IRVINE, DARRELL J.; WUNDERLICH, GERHARD. A multilamellar nanoliposome stabilized by interlayer hydrogen bonds increases antimalarial drug efficacy. Nanomedicine-Nanotechnology Biology and Medicine, v. 22, NOV 2019. (16/19145-7, 17/24267-7, 17/08626-7, 15/17174-7)