Departamento de Parasitologia – ICB

Departamento de Parasitologia

SILVIA BEATRIZ BOSCARDIN

Phone: +55 (11) 3091-7263
Room: 46 
Email: sbboscardin@usp.br
Currículo Lattes

Personal site: http://www.researcherid.com/rid/C-3397-2012

Dr. Silvia Beatriz Boscardin graduated in Biomedical Sciences at the Federal University of São Paulo (1996). She has a master’s degree (1999) and PhD (2003) in Microbiology and Immunology from the Federal University of Sao Paulo. She conducted her postdoctoral studies at the Molecular Immunology Laboratory at The Rockefeller University (New York, United States) between 2003 and 2008. Currently she is an assistant professor at Department of Parasitology / Institute of Biomedical Sciences, University of São Paulo (USP). She has experience in Parasitology and Immunology, with emphasis on the development of vaccination strategies against parasites and viruses. Present projects involve the use of a strategy to target proteins derived from pathogens (more specifically Plasmodium sp. and dengue virus) to dendritic cells (DCs) that are responsible for the activation of the adaptive immune response.
Laboratory of Antigen Targeting to Dendritic Cells

GROUP MEMBERS

Elaine Cristina Matos Vicentin

Kelly Nazaré da Silva Amorim

Marcio Massao Yamamoto

Raquel Hoffmann Panatieri

RESEARCH LINE

Targeting pathogen-derived antigens to dendritic cells in vivo: a new strategy for vaccine development

Dendritic cells (DCs) are critical for the induction of immune responses and also peripheral tolerance. This fact opens up the possibility that these cells may be used as targets of possible manipulations aimed at inducing or suppressing immune responses.
Recently, it was demonstrated that antigens could be delivered directly to DCs. When this occurs in the absence of concomitant inflammatory stimuli, the result in the induction of immunological tolerance. On the other hand, when the antigen is delivered to these same cells in the presence of an inflammatory stimulus, the result is the induction of strong immune responses. Antigen targeting to DCs in vivo is accomplished by the administration of low doses of a recombinant chimeric protein consisting of a monoclonal antibody specific for receptors present on the surface of DCs fused with the antigen of interest. We are currently using monoclonal antibodies that have the ability to bind to the endocytic receptors, known as DEC205 and DCIR2, present on the surface of DCs.
Our studies have shown that these chimeric antibodies, when administered in the presence of adjuvants that can stimulate DCs, are potent immunogens capable of inducing long-lasting humoral and cellular immune responses against the antigen of interest. Partial protection has also been obtained in some models.

PUBLICATIONS

IFN-gama-Induced Priming Maintains Long-Term Strain-Transcending Immunity against Blood-Stage Plasmodium chabaudi Malaria. The Journal of Immunology (1950). , v.191, p.5160 – 5169, 2013

Targeting the Non-structural Protein 1 from Dengue Virus to a Dendritic Cell Population Confers Protective Immunity to Lethal Virus Challenge. PLoS Neglected Tropical Diseases (Online). , v.7, p.e2330 – , 2013

TLR5-dependent immunogenicity of a recombinant fusion protein containing an immunodominant epitope of malarial circumsporozoite protein and the FliC flagellin of Salmonella Typhimurium. Memórias do Instituto Oswaldo Cruz (Impresso). , v.106, p.167 – 171, 2011

Direcionando proteínas derivadas de patógenos para células responsáveis pela ativação da resposta imune. Revista da Biologia. , v.6b, p.12 – 16, 2011

CD4+CD25+Foxp3+ Regulatory T Cells, Dendritic Cells and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?. Infection and Immunity (Print). , v.78, p.4763 – 4772, 2010

CD8+ T cell adjuvant effects of Salmonella FliCd flagellin in live vaccine vectors or as purified protein. Vaccine (Guildford). , v.28, p.1373 – 1382, 2010

Chagas’ disease: an update on immune mechanisms and therapeutic strategies. Journal of Cellular and Molecular Medicine (Print). , v.14, p.1373 – 1384, 2010

Immunogenicity and protective efficacy of a recombinant yellow fever vaccine against the murine malarial parasite Plasmodium yoelii. Vaccine (Guildford). , v.28, p.4644 – 4652, 2010

Impaired Innate Immunity in Tlr4-/- Mice but Preserved CD8+ T Cell Responses against Trypanosoma cruzi in Tlr4-, Tlr2-, Tlr9- or Myd88-Deficient Mice. PLoS Pathogens (Online). , v.6, p.e1000870 – , 2010

Poly(I:C) is an effective adjuvant for antibody and multi-functional CD4+ T cell responses to Plasmodium falciparum circumsporozoite protein (CSP) and anti-DEC-CSP in non human primates. Vaccine (Guildford). , v.28, p.7256 – 7266, 2010

Identification of antigen-presenting dendritic cells in mouse aorta and cardiac valves. Journal of Experimental Medicine. , v.206, p.497 – 505, 2009

Immunologically relevant strain polymorphism in the Amastigote Surface Protein 2 of Trypanosoma cruzi. Microbes and Infection. , v.9, p.1011 – 1019, 2007

Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses. Journal of Experimental Medicine. , v.203, p.599 – 606, 2006

The circumsporozoite protein is an immunodominant protective antigen in irradiated sporozoites. Nature (London). , v.444, p.937 – 940, 2006

The non-palindromic adaptor-PCR method for the identification of the T-cell receptor genes of an interferon-g-secreting T-cell hybridoma specific for trans-sialidase, an immunodominant Trypanosoma cruzi antigen. Brazilian Journal of Medical and Biological Research. , v.39, p.345 – 354, 2006

CD8+-T-cell-dependent control of Trypanosoma cruzi infection in a highly susceptible mouse strain after immunization with recombinant proteins based on amastigote surface protein 2. Infection and Immunity. , v.73, p.6017 – 6025, 2005

Protective immunity against Trypanosoma cruzi infection in a highly susceptible mouse strain after vaccination with genes encoding the amastigote surface protein-2 and trans-sialidase. Human Gene Therapy. , v.15, p.878 – 886, 2004

A DNA-priming protein-boosting regimen significantly improves type 1 immune response but not protective immunity to Trypanosoma cruzi infection in a highly susceptible mouse strain. Immunology and Cell Biology. , v.81, p.121 – 129, 2003

Immunization with cDNA expressed by amastigotes of Trypanosoma cruzi elicits protective immune response against experimental infection. Infection and Immunity. , v.71, p.2744 – 2757, 2003

Importance of CD8 T cell-mediated immune response during intracellular parasitic infections and its implications for the development of effective vaccines. Anais da Academia Brasileira de Ciências. , v.75, p.443 – 468, 2003

CD4 Th1 but not CD4 Th2 clones efficiently activate macrophages to eliminate Trypanosoma cruzi through a nitric oxide dependent mechanism.. Immunology Letters. , v.73, p.43 – 50, 2000

Heterologous expression of Trypanosoma cruzi surface glycoprotein (gp82) in mammalian cells indicates the existence of different signal sequence requirements and processing. The Journal of Eukaryotic Microbiology. , v.46, p.557 – 565, 1999

Heterologous expression of Trypanosoma cruzi surface glycoprotein (gp82) indicates that requirements for glycosylphosphatidyl-inositol anchoring are different in mammalian cells and in trypanosome. Memórias do Instituto Oswaldo Cruz. , v.94, p.527 – 530, 1999

Organization and expression of a multigene family encoding the surface glycoproteins of Trypanosoma cruzi metacyclic trypomastigotes involved in the cell invasion. Memórias do Instituto Oswaldo Cruz. , v.94, p.169 – 171, 1999

Targeting a Plasmodium vivax merozoite surface protein 1 fragment to the DEC205+ dendritic cell population elicits strong antibody and T cell responses.. Frontiers in Immunology. , v.4, p.abstract – , 2013

Targeting the Plasmodium chabaudi MSP-1(19) protein to the DEC205 dendritic cell population induces faster parasite clearance. Frontiers in Immunology. , v.4, p.abstract – , 2013

Influence of different adjuvant formulations in humoral responses after immunization with a HIV envelope glycoprotein trimer. Frontiers in Immunology. , v.4, p.abstract – , 2013

A triple positive staining to capture B cells expressing anti-tetanus toxoid IgG in human blood. Frontiers in Immunology. , v.4, p.abstract – , 2013

Placental lesions as result of TLR4 activation by Plasmodium berghei are associated with low birth weight. Frontiers in Immunology. , v.4, p.abstract – , 2013

Anti-DEC-205 receptor carrying P10 induces protective response in experimental Paracoccidioidomycosis. Frontiers in Immunology. , v.4, p.abstract – , 2013

In Vivo Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria. PLoS Pathogens (Online), v. 11, p. e1004598, 2015

Antigen Targeting to Dendritic Cells Allows the Identification of a CD4 T-Cell Epitope within an Immunodominant Trypanosoma cruzi Antigen. Plos One, v. 10, p. e0117778, 2015

The dengue virus non-structural 1 protein: Risks and benefits. Virus Research (Print). , v.181, p.53 – 60, 2014

Parenteral Adjuvant Effects of an Enterotoxigenic Escherichia coli Natural Heat-Labile Toxin Variant. Frontiers in Immunology (Online). , v.4, p.487 – , 2014

MyD88 Signaling is Directly Involved in the Development of Murine Placental Malaria. Infection and Immunity (Print). , v.82, p.830 – 838, 2013

Capítulos de livros publicados

Recent advances in vaccine development against malaria caused by Plasmodium falciparum In: Plasmodium falciparum: Morphology, Life Cycle and Health Impact.1 ed. Hauppauge, NY : Nova Publishers, 2012, v.1, p. 1-56

Vaccines based on dendritic cell biology. In: New Generation Vaccines.4 ed.New York : Informa Healthcare, 2009, v.1, p. 327-339

RESEARCH PROJECTS/FUNDING

Project Name: Study of protective mechanisms induced by vaccination of mice with fusion antibodies able to target dengue virus proteins to dendritic cells.
Coordinator name: Silvia Beatriz Boscardin
Funding Agency: FAPESP
Start date: 09/2013 – Duration: 08/2015
Título: Instituto Nacional de Ciência e Tecnologia de Vacinas (INCTV). Projeto 15203*12 – CNPq / INCTV.
Vigência: 10/2009 à 10/2014
Agência Financiadora: Conselho Nacional de Desenvolvimento Científico e Tecnológico
Título: Manipulação de células dendríticas para o estudo de interações parasita-hospedeiro nos estágios pré-eritrocíticos da malária
Vigência: 12/2011 à 12/2014
Agência Financiadora: Banco BNP Paribas
Project Name: Using the knowledge generated by the study of pathogenic mechanisms in gestational malaria to develop vaccines that target antigens to dendritic cells
Coordinator name: Silvia Beatriz Boscardin / Claudio Farias Romero Marino
Funding Agency: CAPES
Start date: 01/2011 – Duration: 06/2015
Project Name: IMAGING AND IMPROVEMENT OF IMMUNE PROTECTION AGAINST MALARIA PARASITES (IM3ALARIA)
Coordinator name: Silvia Beatriz Boscardin/Rogério Amino
Funding Agency: FAPESP-ANR
Start date: 11/2014 – Duration: 10/2017

COLLABORATORS

Brazilian Collaborators

  • Prof. Dr. Luís Carlos de Souza Ferreira | ICB/USP, São Paulo
  • Prof. Dr. Claudio Romero Farias Marinho | ICB/USP, São Paulo
  • Profa. Dra. Maria Regina D’Ímperio Lima | ICB/USP, São Paulo
  • Prof. Dr. Marcelo Urbano Ferreira | ICB/USP, São Paulo
  • Profa. Dra. Irene da Silva Soares | FCF/ USP, São Paulo
  • Prof. Dr. Sandro Almeida | FCF/ USP, São Paulo
  • Profa. Dra. Daniela Santoro Rosa | UNIFESP, São Paulo
  • Prof. Dr. Fabio Trindade Maranhão Costa | UNICAMP, Campinas
  • Prof. Dr. Daniel Mansur | UFSC, Florianópolis
  • Prof. Dr. André Mansur | UFSC, Florianópolis
  • Dra. Alda Alves | Fiocruz, Rio de Janeiro
  • Dr. Juliano Bordignon | Fiocruz, Curitiba
  • Dra. Ana Moro | Instituto Butantan, São Paulo
  • Dra. Denise Tambourgui | Instituto Butantan, São Paulo

International Colaborators

  • Dr. Michel Nussenzweig | The Rockefeller University, Estados Unidos
  • Dr. Rogério Amino | Instituto Pasteur, Paris
  • Dr. Robert Menard | Instituto Pasteur, Paris
  • Dra. Hedda Wardemann | Instituto Max-Planck, Alemanha