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Evaluation of the HIV-1 specific cellular immune response, identification of HIV-1 epitopes and role of CD4+CD25+FoxP3+ Regulatory T cells in long-term non progressors (LTNP) and elite controllers (EC) HIV-1 infected individuals

Grant number: 14/09623-3
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2014
Effective date (End): October 31, 2017
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Alberto José da Silva Duarte
Grantee:Bosco Christiano Maciel da Silva
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


The global HIV/Aids pandemic is one of the most important in the last decades. Since it was discovery, Aids have affected more than 60 million people and have killed over 25 million mostly in developing countries. It is a priority to obtain an HIV vaccine or new forms of effective treatments as well as discover new correlates of protection against the virus in all regions of the world. Unfortunately, the main obstacle to get HIV vaccine is the enormous genetic variability of the virus. Long-Term Non Progressors (LTNP) and elite controllers (EC) are between one to 5 % from those infected, these subjects remain asymptomatic, and without signs of Aids progression for a period of time for more than eight to 10 years, the cell counts of CD4+ T cells remain stable and above 500 cells/mm3, without antiretroviral therapy. These individuals are considered "key individuals" in the study of correlates of protection and HIV vaccine. The factors that determine a non-progression or slow progression of the virus in these individuals are not fully understood and have been insufficiently studied in our country. Regulatory T cells (Treg) CD4+CD25+FoxP3+ constitute a subpopulation of T cells that have the ability to suppress the activation and proliferation of T cells and their role in individuals LTNP and EC are very discussed. The T cell responses against HIV have a critical role on the virus control and in the development of vaccines strategies, prophylactic or therapeutic. The vast majority of vaccines studies are target to the induction of T cell responses against epitopes of HIV subtype B. It is important to define the epitopes recognized by T cells of the Brazilian individuals and study the cross-reactivity between different epitopes of HIV subtypes circulating in Brazil, evaluating the viral variability effect on the recognition of these epitopes. Our main aims are: a) to characterize the epidemiological, clinical and laboratory profiles of the 25 LTNP and EC subjects of the HIV-1 cohort; B) to characterize the phenotype of Treg cells (CD4+CD25+FoxP3+) and their influence on T cell activation in individuals LTNP and EC; C) to identify immunodominant HIV-1 epitopes recognized by T cells of LTNP/EC, and determinate the phenotype of T cell (CD4+ or CD8+) involved; D) to determine the T cell cross-reactivity between the B, BBr, C and F epitopes from HIV-1 Brazilian isolates. (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)
LOUREIRO DOS REIS, MARILIA M.; QUEIROZ, MARIA A. F.; DA SILVA, BOSCO C. M.; DA SILVA DUARTE, ALBERTO J.; ARGANARAZ, GUSTAVO A.; VALLINOTO, ANTONIO C. R.; ARGANARAZ, ENRIQUE R.. IL6 and FAS/FASL gene polymorphisms may be associated with disease progression in HIV-1-positive ethnically mixed patients. Journal of Medical Virology, v. 92, n. 8, p. 1148-1157, . (14/09623-3)
MANTOVANI, NATHALIA; DEFELICIBUS, ALEXANDRE; DA SILVA, ISRAEL TOJAL; CICERO, MAIRA FERREIRA; SANTANA, LUIZ CLAUDIO; ARNOLD, RAFAEL; DE CASTRO, DANIELA FUNAYAMA; SANZ DURO, RODRIGO LOPES; NISHIYAMA-JR, MILTON YUTAKA; MEIRELLES JUNQUEIRA-DE-AZEVEDO, INACIO LOIOLA; et al. Latency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response. SCIENTIFIC REPORTS, v. 11, n. 1, . (13/06584-4, 20/10396-2, 13/02652-5, 14/09623-3)

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