Influence of the proteic-energetic malnutrution in the humoral e cellular immune responses elicited by a malaria vaccine in C57Bl/6 mice

• Grant number: 19/25373-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2020
• Effective date (End): April 30, 2022
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Eduardo Lani Volpe da Silveira
• Grantee: Ana Carolina Machado de Faria
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). 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

Abstract

Malaria is a parasitic disease spread out worldwide that afflicts hundreds of million people in tropical areas and kills nearly 0.5 million deaths per year. Seven species of the Plasmodium parasite have been described as the malaria ethiological agents in humans. Among them, Plasmodium vivax (Pv) infections possess the largest prevalence even in Brazil. Usually, the symptoms induced by Pv infection are milder than the ones caused by Plasmodium falciparum (Pf), often found in Africa. A relentless search for a malaria vaccine has been performed for decades. Among the formulations that displayed efficacy in pre-clinical or clinical trials, the majority drives a specific immune response against the pre-erythrocytic forms of the parasite. At this stage of the parasite life cycle, the circumsporozoite protein (CSP) is the most immunogenic antigen. Its structure is folded in 3 domains composed by sequence repeats and B cell epitopes. Due to the high immunogenicity of those repeats, the DNA sequencing of the CSP central domain has pointed out to the presence of mutations depending on the parasite origin. Recently, the research group leaded by Dra. Irene Soares (School of Pharmaceutical Sciences, University of São Paulo) developed a protective vaccine, called yPvCSP-All epitopes, for murine malaria. Its construction has been based in a yeast-expressing recombinant protein coding for the CSP central domain containing the 3 more frequent alleles (VK210, VK247 e P. vivax-like) worldwide. The administration of this recombinant protein adjuvanted by Poly I:C induced not only the detection of T and antibody-secreting cells, but also antibodies specific to all 3 alleles in C57Bl/6 mice under a standard diet. Likewise malaria, malnutrition is a huge public health problem that kills many children around the world, specially in developing countries. During this process, individuals may present a severe immunosuppressive scenario. Among its different types, proteic-energetic malnutrition is the most disseminated. Considering that malnutrition may significantly modify the architecture and function of lymphoid organs, including the bone marrow, it could drastically reduce the ability of antibody secretion by plasma cells. Therefore, the main aim of this project is to evaluate whether the vaccine-derived immune response with the formulation yPvCSP-All epitopes + Poly I:C is the same in C57Bl/6 mice under a standard or proteic-energetic-deficient diet.