Pharmacological effect of the mTOR inhibitor rapamycin in response to memory CD8+ t lymphocytes induced by genetic immunization using heterologous prime-boost

• Grant number: 14/19422-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2014
• End date: August 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• 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

Abstract

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- as a powerful strategy to elicit CD8+ T cell, mainly CD8+ T effector memory cells (TEM), that mediated protective immunity against this parasite. Specific TEM cells with CD44High, CD11aHigh, CD62LLow, KLRG1High e CD127High phenotype are polyfunctional, because secrete IFN-³ and TNF, 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 CD8+ 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 T lymphocytes and especially the TCM phenotype induced by vaccination regimen type of heterologous prime-boost. If this works, this strategy can be used to improve the efficiency of this and other vaccinations. (AU)

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)

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, MAY 25 2021. (18/15607-1, 16/02840-4, 15/08814-2, 14/19422-5, 12/22514-3)

FERREIRA, CAMILA PONTES; CARISTE, LEONARDO MORO; VIRGILIO, FERNANDO DOS SANTOS; MORASCHI, BARBARA FERRI; MONTEIRO, CAROLINE BRANDAO; VIEIRA MACHADO, ALEXANDRE M.; GAZZINELLI, RICARDO TOSTES; BRUNA-ROMERO, OSCAR; MENIN RUIZ, PEDRO LUIZ; RIBEIRO, DANIEL ARAKI; et al. LFA-1 Mediates Cytotoxicity and Tissue Migration of Specific CD8(+) T Cells after Heterologous Prime-Boost Vaccination against Trypanosoma cruzi Infection. FRONTIERS IN IMMUNOLOGY, v. 8, OCT 13 2017. (17/11499-7, 14/19422-5, 15/08814-2, 12/22514-3)