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Role of pharmacological inhibitor mTOR rapamycin in response of memory CD8+ T cells induced by heterologous prime-boost immunization

Grant number: 16/02840-4
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): March 01, 2018
Effective date (End): July 31, 2019
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Jose Ronnie Carvalho de Vasconcelos
Grantee:Barbara Ferri Moraschi
Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Heterologous prime-boost vaccination using plasmid DNA followed by replication defective human recombinant adenovirus type 5 - both expressing the amastigote surface protein 2 (ASP-2) of Trypanosoma cruzi- is a powerful strategy to elicit CD8+ T cells, mainly CD8+ T effector memory cells (TEM), that mediated protective immunity against the parasite protozoan Trypanosoma cruzi. Specific TEM cells with CD44High, CD11aHigh, CD62LLow, KLRG1High e CD127High phenotype are polyfunctional, because secrete IFN-g and TNF-a, mediate cytotoxicity, can remain for a long time and are resistant to immune erosion. Despite the high frequency of specific TEM CD8+ cells induced by this type of vaccination, seek new strategies that can further increase the frequencies of specific T cells and especially the with TCM phenotype (CD44High, CD11aHigh, CD62LHigh and CD127High). A possible strategy in this regard is the use of pharmacological mTOR (rapamycin target protein in mammals) inhibitor, called rapamycin. Treatment with this drug, which is commercially available and approved for human use, were able to increase the frequency of TCM CD8+ in some experimental models of viral infections. Based on these data, the aim of this project will test whether treatment with rapamycin can increase the frequency of specific memory CD8 T cells induced by heterologous "prime-boost" vaccination. If this works, this strategy can be used to improve the efficiency of this and other vaccinations. (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)
PONTES FERREIRA, CAMILA; MORO CARISTE, LEONARDO DE; HENRIQUE NORONHA, ISAU; FERNANDES DURSO, DANIELLE; LANNES-VIEIRA, JOSELI; RAMALHO BORTOLUCI, KARINA; ARAKI RIBEIRO, DANIEL; GOLENBOCK, DOUGLAS; GAZZINELLI, RICARDO TOSTES; VASCONCELOS, JOSE RONNIE CARVALHO DE. CXCR3 chemokine receptor contributes to specific CD8(+) T cell activation by pDC during infection with intracellular pathogens. PLoS Neglected Tropical Diseases, v. 14, n. 6, . (18/15607-1, 15/08814-2, 19/17994-5, 16/02840-4)
MORASCHI, BARBARA FERRI; NORONHA, ISAU HENRIQUE; FERREIRA, CAMILA PONTES; CARISTE, LEONARDO M.; MONTEIRO, CAROLINE B.; DENAPOLI, PRISCILA; VRECHI, TALITA; PEREIRA, GUSTAVO J. S.; GAZZINELLI, RICARDO T.; LANNES-VIEIRA, JOSELI; et al. Rapamycin Improves the Response of Effector and Memory CD8(+) T Cells Induced by Immunization With ASP2 of Trypanosoma cruzi. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, . (18/15607-1, 16/02840-4, 15/08814-2, 14/19422-5, 12/22514-3)
FERREIRA, CAMILA PONTES; CARISTE, LEONARDO MORO; MORASCHI, BARBARA FERRI; ZANETTI, BIANCA FERRARINI; HAN, SANG WON; RIBEIRO, DANIEL ARAKI; MACHADO, ALEXANDRE VIEIRA; LANNES-VIEIRA, JOSELI; GAZZINELLI, RICARDO TOSTES; CARVALHO VASCONCELOS, JOSE RONNIE. CXCR3 chemokine receptor guides Trypanosoma cruzi-specific T-cells triggered by DNA/adenovirus ASP2 vaccine to heart tissue after challenge. PLoS Neglected Tropical Diseases, v. 13, n. 7, . (16/02840-4, 17/11499-7, 12/22514-3, 18/15607-1, 15/08814-2)

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