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Targeting the Plasmodium vivax and Plasmodium yoelii MSP-119 proteins to dendritic cells in vivo: analysis of cellular and humoral immune responses.

Grant number: 09/12625-0
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): March 01, 2010
Effective date (End): August 31, 2011
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Silvia Beatriz Boscardin
Grantee:Icaro Matioli Barbosa
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:07/08648-9 - Recombinant antigen targeting to dendritic cells in vivo: a new strategy for the development of vaccines, AP.JP

Abstract

Malaria is considered the most important parasitic disease of our time and is responsible for 300-600 million clinical cases resulting in 1-3 million deaths per year around the world. Plasmodium vivax (P. vivax) is the second most prevalent malaria causing species worldwide, occurring mainly in South and Southeast Asia, Western Pacific, Eastern Mediterranean and in Central and South America. In the latter, P. vivax is responsible for more than 70% of malaria cases. Even though P. yoelii is a species of Plasmodium that infects mice, it has been widely used in model studies because it presents similar characteristics to the species of Plasmodium that cause human malaria. One of the major proteins expressed on the surface of merozoites of different Plasmodium species is the MSP-1. At the time of erythrocyte invasion this protein undergoes a series of proteolytic cleavages generating a 19 kDa fragment known as MSP-1.19. This protein is a target for neutralizing antibodies and has been studied intensely in immunization protocols, consisting in one of the candidate antigens in the formulation of a vaccine against the erythrocytic stages of malaria. Dendritic cells (DCs) are immune system cells very important in the process of inducing immunity against pathogens. They are able to connect the innate and acquired immune responses and lead to the activation of T and B cells important in the control of infection. Recently it was shown that one can target antigens directly to DCs in vivo by administration of low doses of a recombinant chimeric protein consisting of a monoclonal antibody specific for receptors present on the surface of these cells fused with the antigen of interest. When these chimeric antibodies were injected into animals in the presence of a maturation stimulus for DCs, a strong immune response was obtained against different antigens. Two of the antibodies used have the ability to bind to the endocytic receptors DEC205 and DCIR2 present on the surface of two distinct subpopulations of DCs. Therefore, the main objective of this project is to use the chimeric antibodies against the receptors mentioned above in fusion with the protein MSP-1.19 of P. vivax and P. yoelii, which causes murine malaria.

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BARBOSA, Icaro Matioli. Targeting Plasmodium vivax and Plasmodium yoelii MSP-119 proteins to dendritic cells in vivo: analysis of cellular and humoral immune responses.. 2011. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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