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Mechanism of Generation of humoral immune response induced by targeting of MSP1(19)-PADRE antigen to two different subsets of dendritic cells via DEC205 and DCIR2 receptors

Grant number: 15/18874-2
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): December 01, 2015
Effective date (End): August 31, 2017
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Silvia Beatriz Boscardin
Grantee:Fernando Bandeira Sulczewski
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


There are mainly two Dendritic cells (DCs) subsets in murine spleen, one of them express the endocitic receptor CD205 (DEC205) and the alpha chain of CD8 receptor (DEC205+CD8±+) and the other one express the endocitic receptor DCIR2 but not CD8± (DCIR2+CD8±-). DEC205+CD8±+ DC subset is specialized in antigen cross presentation and CD8+ T cells priming and DCIR2+CD8±- DCs is associated with priming of CD4+ T cells. Targeting antigen to these two DCs subsets via monoclonal antibodies (mAbs) linked with antigenic proteins has been demonstrating good results as an efficient strategy to enhance the immunogenicity of recombinant proteins. Nevertheless, mechanisms of activation of humoral immune response as well as cell interactions induced by theses strategy of vaccination has not been completely clear yet. Thus, this study aims analyses humoral immune response and cell interactions among DCs, T and B cells induced by targeting a model antigen to two DCs subsets. We will use a chimeric mAbs fused in a hybrid protein, which is a portion of 19kDa of merozoite surface protein 1 (MSP119) expressed by Plasmodium vivax associated with PADRE (Pan allelic DR epitope) linked at a quimeric mAbs. The generation of immune response induced by these immunization protocol, the stimulus of booting antigen in enhancement and the influence of cells that express DEC205 or DCIR2 in antibodies will be analyzed. The study of theses mechanisms can help in optimization of vaccines to increase protein antigens immunogenicity.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SULCZEWSKI, FERNANDO BANDEIRA; MARTINO, LARISSA ALVES; ALMEIDA, BIANCA DA SILVA; ZANETI, ARTHUR BARUEL; FERREIRA, NATALIA SOARES; DA SILVA AMORIM, KELLY NAZARE; YAMAMOTO, MARCIO MASSAO; APOSTOLICO, JULIANA DE SOUZA; ROSA, DANIELA SANTORO; BOSCARDIN, SILVIA BEATRIZ. Conventional type 1 dendritic cells induce T(H)1, T(H)1-like follicular helper T cells and regulatory T cells after antigen boost via DEC205 receptor. European Journal of Immunology, v. 50, n. 12, . (18/20821-2, 15/18874-2, 17/06503-5, 15/16565-2, 18/00145-2, 18/07142-9)
ANTONIALLI, RENAN; SULCZEWSKI, FERNANDO BANDEIRA; DA SILVA AMORIM, KELLY NAZARE; ALMEIDA, BIANCA DA SILVA; FERREIRA, NATALIA SOARES; YAMAMOTO, MARCIO MASSAO; SOARES, IRENE SILVA; DE SOUZA FERREIRA, LUIS CARLOS; ROSA, DANIELA SANTORO; BOSCARDIN, SILVIA BEATRIZ. CpG Oligodeoxinucleotides and Flagellin Modulate the Immune Response to Antigens Targeted to CD8 alpha(+) and CD8 alpha(-) Conventional Dendritic Cell Subsets. FRONTIERS IN IMMUNOLOGY, v. 8, . (14/50631-0, 13/11442-4, 15/18874-2)
ZANETI, ARTHUR BARUEL; YAMAMOTO, MARCIO MASSAO; SULCZEWSKI, FERNANDO BANDEIRA; ALMEIDA, BIANCA DA SILVA; SANTOS SOUZA, HIGO FERNANDO; FERREIRA, NATALIA SOARES; NASCIMENTO FABRIS MAEDA, DENICAR LINA; SALES, NATIELY SILVA; ROSA, DANIELA SANTORO; DE SOUZA FERREIRA, LUIS CARLOS; et al. Dendritic Cell Targeting Using a DNA Vaccine Induces Specific Antibodies and CD4(+) T Cells to the Dengue Virus Envelope Protein Domain III. FRONTIERS IN IMMUNOLOGY, v. 10, . (16/04477-4, 13/11442-4, 14/50631-0, 14/17595-0, 15/16565-2, 14/15061-8, 15/18874-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SULCZEWSKI, Fernando Bandeira. Mechanism of generation of humoral immune response induced by targeting of MSP119PADRE antigen to two different subsets of dendritic cells via DEC205 and DCIR2 receptors.. 2017. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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