Production of chimeric monoclonal antibodies capable of directing the MSP142 protein from Plasmodium yoelii to different dendritic cell populations

• Grant number: 14/00594-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): April 01, 2014
• Effective date (End): March 31, 2015
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Silvia Beatriz Boscardin
• Grantee: Juliana Martins Stopa
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Dendritic cells (DCs) are key in the process of induction of immunity and tolerance against various pathogens. DCs can be divided into different populations according to the expression surface markers. In the mouse spleen and lymph nodes, there are 2 distinct populations: one expressing the DEC205 endocytic receptor and the alpha chain of the CD8 molecule (DEC205+CD8±+ DCs ) and another expressing the DCIR2 receptor and not express the alpha chain of the CD8 molecule (DCIR2+CD8±- DCs). The literature indicates that these populations have different functions with respect to their ability to induce immune responses against different pathogens. The possibility of manipulating these cells for the generation of an anti-pathogen immune response is quite interesting and different groups have achieved promising results. Recently, a strategy for targeting antigens to DCs in vivo has been developed successfully in animal models. This strategy uses a monoclonal antibody (mAb ) against a receptor present on the surface of the DC infusion with the antigen of interest. The administration of low doses of this chimeric mAb in the presence of DC maturation stimuli is able to activate antigen-specific T cells, induce the production of high antibody titers and induce protection against challenge with the pathogen in certain models. Malaria is a major public health problem and occurs in approximately 100 countries. It is a parasitic disease caused by protozoa of the genus Plasmodium and transmitted by mosquitoes of the genus Anopheles, which presents high rates of morbidity and mortality. Animal models have been used to understand the biology of the parasite-host interaction, the pathogenesis of the disease, and also for the development of vaccines against the parasite. One of the most used animal models is the combination Plasmodium yoelli - mice. This parasite infects all strains of mice and induces a disease similar to that caused by Plasmodium falciparum, which is the main species that causes mortality in the human population. Parasite proteins expressed on the surface of infected erythrocytes and merozoites ( infective forms for the erythrocytes), such as the merozoite surface protein 1 (MSP1), are considered priority antigens for the development of a vaccine against the blood stages of Plasmodium. The C-terminal fragment of this protein that has 42 kDa ( MSP142 ) is of particular interest because it is able to activate CD4+ T lymphocytes and B lymphocytes to produce antibodies. In this project, we intend to clone the MSP142 protein sequence of P. yoelli fused to anti-DEC205 and anti-DCIR2 mAbs and produce both chimeric mAbs by transient transfection of eukaryotic cells.(AU)