Analyzing the effector mechanisms in the Th1/Th2 poles of the Radiation-Attenuated (RA) Schistosoma Vaccine model by Systems Vaccinology

• Grant number: 12/18095-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2012
• End date: November 30, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Luciana Cezar de Cerqueira Leite
• Grantee: Juliana Vitoriano de Souza
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

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. However, studies have shown that chemotherapy does not prevent reinfection in endemic areas and in some cases there are reports of the existence of drug-resistant parasites. In this sense, the use of anti-Schistosoma vaccine becomes interesting and represents an effective and inexpensive control of this disease, preventing the emergence of parasites resistant and significantly reducing the morbidity, the reinfection risk and spread of the disease. One of the major challenges in developing a vaccine against schistosomiasis is the selection of potential antigens, due to factors related to the complexity of the parasite life cycle and the presence of different mechanisms of immune evasion. In addition to these factors, we still have a limited comprehension of the protective mechanisms associated with resistance in animal models after immunization with attenuated parasites. So far, most vaccinology studies have been based on empirical approaches, where the early events that direct protective immunity against a particular pathogen are unclear and not exploited.In this context, this project aims to reanalyze the model of radiation-attenuated cercaria, through the comparison of activated/repressed gene networks of total peripheral monuclear 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 and subunit vaccines.

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)

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, MAR 11 2021. (12/23124-4, 12/18095-5)

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, DEC 2015. (12/23124-4, 14/09361-9, 12/18095-5)

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., 2015-12-01. (12/23124-4, 12/18095-5, 14/09361-9)