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Investigating the effector mechanisms of the Schistosoma mansoni attenuated vaccine by Systems Vaccinology

Grant number: 12/23124-4
Support Opportunities:Regular Research Grants
Duration: May 01, 2013 - April 30, 2018
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Luciana Cezar de Cerqueira Leite
Grantee:Luciana Cezar de Cerqueira Leite
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated researchers:Helder Takashi Imoto Nakaya ; Luciana Cezar de Cerqueira Leite ; Paulo Lee Ho ; Robert Alan Wilson ; Sergio Verjovski Almeida

Abstract

Vaccination is one of the greatest triumphs of modern medicine, yet we remain largely ignorant of the mechanisms by which successful vaccines stimulate protective immunity. The grand challenge for biology and medicine at the turn of the 21st century is to understand the biological complexity that emerges from interactions between our immune system and the environment (e.g. pathogens). To tackle this challenge, a "holistic" rather than solely reductionist approach should be used; to obtain predictive, rather than descriptive data. This strategy became possible due to the development of new technologies for measuring and visualizing the behavior of large gene dataset, using computational and mathematical tools for dealing with complex data sets. In this context, systems Vaccinology emerged as an interdisciplinary area that combines the measure of multiple parameters; and its analysis through interacting networks and predictive modeling applied to vaccines. This approach has already been applied to investigate viral commercial vaccines (attenuated/inactivated) and has enabled the identification of early innate signatures that predict the immunogenicity of these vaccines, as well as, potentially novel mechanisms of immune regulation.Schistosomiasis is an important diseases caused by trematode worms of the genus Schistosoma, affecting more than 200 million people worldwide in 74 countries. This parasitic disease is a serious public health problem, where several control measures are proposed, among which stands out treatment with the anthelmintic drug, praziquantel and the development of a vaccine. One of the major challenges in developing a vaccine against schistosomiasis is the limited comprehension of the protective mechanisms associated with resistance in animal models after immunization with attenuated parasites. In this context, this project aims to analyze the model of radiation-attenuated cercaria, through the comparison of activated/repressed gene networks of total peripheral mononuclear cells (PBMC) and sdLN (skin draining lymph nodes) from immunized mice with one dose (inducing a Th1-predominant immune response), three doses (inducing a Th2-predominant immune response) and infected with normal parasites (Th0). To do this, we intend to use a microarray platform, together with multiplex analysis of cytokines, and multiparameter ow cytometry. This data will help in the search for correlates of protection, or more appropriately, signatures of innate and adaptive immunity required for activation of the protective immune response. Thus, new mechanisms of action and prediction of immunogenicity and vaccine efficacy could be revealed on the molecular basis, allowing the future design of novel delivery systems and adjuvants for recombinant subunit vaccines. (AU)

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Scientific publications (8)
(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)
FARIAS, LEONARDO PAIVA; VITORIANO-SOUZA, JULIANA; CARDOZO, LUCAS ESTEVES; GAMA, LEONARDO DOS REIS; SINGH, YOUVIKA; MIYASATO, PATRICIA AOKI; ALMEIDA, GIULLIANA TESSARIN; RODRIGUEZ, DUNIA; FERRARI BARBOSA, MAYRA MARA; FERNANDES, RAFAELA SACHETTO; et al. Systems Biology Analysis of the Radiation-Attenuated Schistosome Vaccine Reveals a Role for Growth Factors in Protection and Hemostasis Inhibition in Parasite Survival. FRONTIERS IN IMMUNOLOGY, v. 12, . (12/23124-4, 12/18095-5)
FARIAS, LEONARDO P.; VANCE, GILLIAN M.; COULSON, PATRICIA S.; VITORIANO-SOUZA, JULIANA; NETO, ALMIRO PIRES DA SILVA; WANGWIWATSIN, ARPORN; NEVES, LEANDRO XAVIER; CASTRO-BORGES, WILLIAM; MCNICHOLAS, STUART; WILSON, KEITH S.; et al. Epitope Mapping of Exposed Tegument and Alimentary Tract Proteins Identifies Putative Antigenic Targets of the Attenuated Schistosome Vaccine. FRONTIERS IN IMMUNOLOGY, v. 11, . (12/23124-4, 17/24832-6)
FERNANDES, RAFAELA SACHETTO; BARBOSA, TEREZA CRISTINA; FERRARI BARBOSA, MAYRA MARA; MIYASATO, PATRICIA AOKI; NAKANO, ELIANA; CERQUEIRA LEITE, LUCIANA CEZAR; FARIAS, LEONARDO PAIVA. Stage and tissue expression patterns of Schistosoma mansoni venom allergen-like proteins SmVAL 4, 13, 16 and 24. PARASITES & VECTORS, v. 10, . (12/23124-4, 10/18486-9)
FERNANDES, RAFAELA S.; FERNANDES, LUIS G. V.; DE GODOY, ANDRE S.; MIYASATO, PATRICIA A.; NAKANO, ELIANA; FARIAS, LEONARDO P.; NASCIMENTO, ANA L. T. O.; LEITE, LUCIANA C. C.. Schistosoma mansoni venom allergen-like protein 18 (SmVAL18) is a plasminogen-binding protein secreted during the early stages of mammalian-host infection. Molecular and Biochemical Parasitology, v. 221, p. 23-31, . (12/23124-4, 10/18486-9)
KANNO, ALEX ISSAMU; DE CERQUEIRA LEITE, LUCIANA CEZAR; PEREIRA, LENNON RAMOS; RODRIGUES DE JESUS, MONICA JOSIANE; ANDREATA-SANTOS, ROBERT; DOS SANTOS ALVES, RUBENS PRINCE; DURIGON, EDISON LUIZ; DE SOUZA FERREIRA, LUIS CARLOS; GONCALVES, VIVIANE MAIMONI. Optimization and scale-up production of Zika virus Delta NS1 in Escherichia coli: application of Response Surface Methodology. AMB EXPRESS, v. 10, n. 1, . (12/23124-4, 14/17595-0, 16/20045-7)
WILSON, R. ALAN; LI, XIAO HONG; MACDONALD, SANDY; NEVES, LEANDRO XAVIER; VITORIANO-SOUZA, JULIANA; LEITE, LUCIANA C. C.; FARIAS, LEONARDO P.; JAMES, SALLY; ASHTON, PETER D.; DEMARCO, RICARDO; et al. The Schistosome Esophagus Is a `Hotspot' for Microexon and Lysosomal Hydrolase Gene Expression: Implications for Blood Processing. PLoS Neglected Tropical Diseases, v. 9, n. 12, . (12/23124-4, 14/09361-9, 12/18095-5)
FARIAS, LEONARDO P.; CHALMERS, LAIN W.; PERALLY, SAMIRAH; ROFATTO, HENRIQUE K.; JACKSON, COLIN J.; BROWN, MARTHA; KHOURI, I, MARIANA; BARBOSA, MAYRA M. F.; HENSBERGEN, PAUL J.; HOKKE, CORNELIS H.; et al. Schistosoma mansoni venom allergen-like proteins: phylogenetic relationships, stage-specific transcription and tissue localization as predictors of immunological cross-reactivity. International Journal for Parasitology, v. 49, n. 8, p. 593-599, . (12/23124-4, 08/57946-5, 07/07685-8)
WILSON, R. ALAN; LI, XIAO HONG; MACDONALD, SANDY; NEVES, LEANDRO XAVIER; VITORIANO-SOUZA, JULIANA; LEITE, LUCIANA C. C.; FARIAS, LEONARDO P.; JAMES, SALLY; ASHTON, PETER D.; DEMARCO, RICARDO; et al. The Schistosome Esophagus Is a 'Hotspot' for Microexon and Lysosomal Hydrolase Gene Expression: Implications for Blood Processing. PLoS Neglected Tropical Diseases, v. 9, n. 12, p. 25-pg., . (12/23124-4, 12/18095-5, 14/09361-9)

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