Preclinical tests of recombinant adenovirus-based protein and vaccine formulations expressing the Plasmodium vivax circumsporozoite protein

• Grant number: 14/18102-7
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): October 01, 2014
• Effective date (End): January 31, 2019
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Irene da Silva Soares
• Grantee: Alba Marina Gimenez
• Home Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 12/13032-5 - Generation and analysis of the immunogenicity of recombinant proteins based on the different allelic forms of the circumsporozoite antigen of Plasmodium vivax aiming at the development of a universal vaccine against malaria, AP.TEM
• Associated scholarship(s): 16/26123-0 - Analysis of protective immunity of vaccine formulations against Plasmodium vixax after challenge with P. berghei/P. vivax transgenic parasites in murine model, BE.EP.PD

Abstract

Plasmodium vivax is the second most prevalent species causing malaria in the world. Currently, there are 132-391 million of estimated cases per year. The relative inefficiency of control actions currently employed requires the development of new prevention strategies, such as vaccines, new drugs and new insecticides. Studies were performed in the past 20 years for development of a recombinant vaccine against human infection by Plasmodium falciparum antigens, based on the circumsporozoite protein (CS). A clinical phase III trials recently published, conducted with African children, reported an efficacy of about 50%. Based on studies with P. falciparum, our goal during the previous thematic project was the production of recombinant proteins and adenovirus based on primary sequences of different allelic forms of P. vivax CS protein. These proteins and adenovirus have been successfully used in heterologous prime-boost (adenovirus/recombinant protein)vaccination protocols in experimental models of mice. These protocols were able to induce immunity against the three allelic forms of the CS protein of P. vivax. These recombinants and their vaccination protocols were objects of a patent application from our group recently submitted to the United States Patent and Trademark Office ("Plasmodium vivax vaccine compositions WO2013142278-A1"). In this project, currently funded by the Thematic Project 2012 / 13032-5, our goal will be to continue our studies for the development of a universal vaccine against P. vivax. As part of the immunization with proteins and recombinant adenovirus based on the CS protein of Plasmodium vivax, it is our aim to further characterize the immunogenicity of experimental vaccination with recombinant proteins and adenoviruses. For that, the following steps are intended to be performed: 1) Expression, purification and characterization of a recombinant protein expressed in P. pastoris containing the three repeat regions of the CS protein of P. vivax; 2) Expression, purification and characterization of a recombinant protein expressed in P. pastoris containing the three repeat regions of the P. vivax CS protein fused with the nucleoprotein of the mumps virus as a virion-like particles (VLPs); 3) Expansion of recombinant adenoviruses containing the three repeat regions of the CS protein of P. vivax in HEK 293 cells and further purification; 4) Use of protein and recombinant adenovirus vaccination in homologous (protein / protein) and heterologous (adenovirus / protein) vaccination protocols in inbred mice for analysis of protective immunity after challenge with P. berghei parasites expressing the CS protein of P. vivax. We hope to the end of this project have the demonstration of in vivo biological effect of our recombinant vaccines. This fact opens the possibility of producing these in cGMP conditions for testing in man.

Scientific publications

(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)

DE CAMARGO, TARSILA MENDES; DE FREITAS, ELISANGELA OLIVEIRA; GIMENEZ, ALBA MARINA; LIMA, LUCIANA CHAGAS; CARAMICO, KARINA DE ALMEIDA; FRANCOSO, KATIA SANCHES; BRUNA-ROMERO, OSCAR; ANDOLINA, CHIARA; NOSTEN, FRANCOIS; RENIA, LAURENT; ERTL, HILDEGUND C. J.; NUSSENZWEIG, RUTH S.; NUSSENZWEIG, VICTOR; RODRIGUES, MAURICIO M.; REYES-SANDOVAL, ARTURO; SOARES, IRENE S. Prime-boost vaccination with recombinant protein and adenovirus-vector expressing Plasmodium vivax circumsporozoite protein (CSP) partially protects mice against Pb/Pv sporozoite challenge. SCIENTIFIC REPORTS, v. 8, JAN 18 2018. Web of Science Citations: 3.