Generation of chimeric recombinant proteins for vaccine development against Plasmodium vivax

Abstract

Plasmodium vivax is the most world-widely distributed and the most prevalent species in America. Vaccine development for P. vivax is considered a priority in the global program for the eradication of malaria. In contrast to P. falciparum, currently, there are no human vaccine trials described against infection to P. vivax. We hypothesize that an effective vaccine formulation should be composed by immunodominant regions of two or more antigens of the parasite. Based on that, our aim in this project is to generate chimeric recombinant proteins based on selected immunodominant domains of the P. vivax infective forms, merozoites. For that purpose, we selected the Apical Membrane Antigen 1 (AMA-1) and the C-terminal region of Merozoite Surface Protein 1 (MSP-1) which we previously characterized as highly immunogenic in natural infections. Chimeric proteins will be expressed in the yeast Pichia pastoris using synthetic codon-optimized genes. We will evaluate the expression and establish the purification procedure. If successful, we will use these proteins for pre-clinical vaccinations in mice. The analysis of the immune response will be evaluated by serum IgG antibodies detection (ELISA) against bacterial recombinant proteins representing each one of them or the chimeric protein. This will allow us to conclude whether, in fact, the use of chimeric antigens provides an advantage to enhance antibody response to immunodominant antigens.(AU)