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Mechanism of immune recognition and antigen enhanced by gamma radiation processing in toxoplasmosis

Grant number: 14/17029-4
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2015
Effective date (End): December 31, 2018
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Heitor Franco de Andrade Junior
Grantee:Andrea da Costa
Host Institution: Instituto de Medicina Tropical de São Paulo (IMT). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Diseases caused by protozoa Apicomplexa such malaria and toxoplasmosis are disseminated and with low protection against reinfection despite disease protection. Vaccines with irradiated parasites showed very promising results in 1967, but after nearly 50 years of research, an alternative offers no effective progress. In toxoplasmosis, vaccines with irradiated agents promote immunity to the disease similar to previous infection. Radiation prevents agent replication but keeps its physiology exposing correct antigens for immune response. We also demonstrated that isolated irradiated Toxoplasma antigens induced better immunity without associated adjuvant, showing that radiation must act also on isolated proteins and not only nucleic acids. Main steps of immune response are antigen presentation by cells (APCs), expansion of responsive T and B clones, and selection of high affinity clones. The effect of radiation must modify recognition and presentation of antigens by cells that could be due to either aggregation of antigens and lower solubility; or targeting to receptors with improved uptake; or even improper or prolonged intracellular processing. In this project, we aim to elucidate these mechanisms analyzing cell uptake of biosynthetically labeled Toxoplasma antigens after irradiation, using macrophages or APCs genetically deficient in scavenger receptor or in the presence of specific receptor blockers. This may result in the production of a potentially more efficient and safe vaccine for human or veterinary toxoplasmosis, preventing disease and improving meat quality for human intake. In an extended view, the use of radiation in human vaccines could be a simple and feasible form to avoid the use of adjuvants. (AU)

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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)
DA COSTA, ANDREA; DE ANDRADE JR, HEITOR FRANCO. Toxoplasma gondii in CD36-/- mice shows lethal infection and poor immunization with probable macrophage immune defects. Parasitology Research, v. N/A, p. 9-pg., . (13/04676-9, 14/17029-4)
DA COSTA, ANDREA; DO NASCIMENTO, NANCI; GALISTEO, JR., ANDRES JIMENEZ; DIAS DOS PASSOS, ALINE BASTOS; DE ANDRADE, JR., HEITOR FRANCO. Radiation effects on Toxoplasma antigens: different immune responses of irradiated intact tachyzoites or soluble antigens in experimental mice models. International Journal of Radiation Biology, v. 96, n. 5, . (14/17029-4)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
COSTA, Andrea da. Mechanism of recognition and immune processing of antigens enhanced by radiation gamma in toxoplasmosis. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Medicina Tropical de São Paulo (IMT) São Paulo.

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