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Comparative analysis between the humoral and cellular immune responses elicited by a malaria vaccine adjuvanted with poly I:C or alum in C57BL/6 mice

Grant number: 19/06494-1
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2019
Effective date (End): May 31, 2021
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Eduardo Lani Volpe da Silveira
Grantee:Tiffany Bianca Lage da Costa
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, causing annually nearly 0.5 million deaths. Five species of the Plasmodium parasite have been described as the malaria ethiological agents in humans. 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) which is often found in Africa. A relentless search for a malaria vaccine has been performed for decades. Most of the formulations that displayed efficacy in pre-clinical or phase 1-2 clinical trials drive 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 that contain sequence repeats and B cell epitopes. Due to the high immunogenicity of those repeats, the DNA sequencing of the CSP central domain have 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 recombinant protein coding for the CSP central domain containing the 3 more frequent alleles (VK210, VK247 e P. vivax-like) in the worldwide. Associated to this protective response, antibodies and T cells specific to all 3 alleles were detected upon immunization. This promising result was obtained upon the administration of yPvCSP-All epitopes recombinant protein and Poly I:C in C57Bl/6 mice. Few adjuvants have been licensed for human use and the most frequent chosen has been the aluminium hydroxide, also known as Alum. Different combinations of antigen and adjuvant may alter the immunogenicity and, subsequently, the effectiveness of a vaccine. Therefore, our project aim is to compare the humoral and cellular immune responses derived of 3-dose vaccination with yPvCSP-All epitopes recombinant protein adjuvanted with Poly I:C or Alum in C57Bl/6 mice.

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