Identification of virological, genetic and immunological factors associated with the phenotype of HIV disease non-progression: a study of HIV virulence markers, CCR5 co-receptor genotyping and expression of broad panel of cytokines (cDNA microarrays) in peripheral blood samples of patients with HIV progressors and non-progressors followed up at Casa da AIDS [SIDA Healthcare Services]

• Grant number: 01/00729-3
• Support Opportunities: Regular Research Grants
• Duration: August 01, 2001 - October 31, 2005
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Edecio Cunha Neto
• Grantee: Edecio Cunha Neto
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Experimental HIV-1vaccines which underwent clinical assessment in humans so far had limited or no success, and progress in epitope constitution may help improve vaccine efficacy. To identify immunodominant and potentially protective human CD4+ T cell epitopes in HIV-1, we used the TEPITOPE algorithm to screen the most conserved regions of the whole genome of HIV-1 subtype B consensus sequence, that would most likely bind multiple HLA-DR molecules and tested their recognition by T cells from sensitized individuals. The eighteen most promiscuous peptides were selected and the actual promiscuity of HLA binding was assessed by direct assays to 9 prevalent HLA-DR molecules. Synthetic peptides were tested with IFN-y ELISPOT assays on peripheral blood mononuclear cells (PBMC) from chronically HIV-1 infected patients (8 long-term nonprogressors (LTNP) and 24 under antiretroviral treatment) and 8 uninfected controls. PBMC from 29 out of the 32 HIV-1+ patients (91%) recognized at least one of the promiscuous peptides, while none of the healthy controls recognized peptides. All 18 peptides were recognized, and each peptide was recognized by at least 7 patients; 44% of the patients recognized 5 or more peptides, and 19% of patients recognized 10 or more peptides. A combination of the three most frequently recognized peptides elicited responses in 75% of patients. Similar responses were obtained in CD8+ T cell-depleted PBMC, and apparently this response was not associated to particular HLA-DR alleles. In silico prediction of promiscuous epitopes led to the identification of naturally immunodominant CD4+ T cell epitopes recognized by PBMC from a significant proportion of a genetically heterogeneous patient population exposed to HIV-1. This combination of CD4+ T cell epitopes – 11 of them not described before – may have the potential for inclusion in a vaccine against HIV-1, allowing the immunization of genetically distinct populations. (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)

P.C. TEIXEIRA; L.K. IWAI; A.C.K. KURAMOTO; R. HONORATO; A. FIORELLI; N. STOLF; J. KALIL; E. CUNHA-NETO. Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy. Brazilian Journal of Medical and Biological Research, v. 39, n. 12, p. 1549-1562, 2006-10-30. (01/00729-3, 00/14549-4)

FONSECA‚ S.G.; COUTINHO-SILVA‚ A.; FONSECA‚ L.A.M.; SEGURADO‚ A.C.; MORAES‚ S.L.; RODRIGUES‚ H.; HAMMER‚ J.; KALLÁS‚ E.G.; SIDNEY‚ J.; SETTE‚ A.; et al. Identification of novel consensus CD4 T-cell epitopes from clade B HIV-1 whole genome that are frequently recognized by HIV-1 infected patients. AIDS, v. 20, n. 18, p. 2263-2273, 2006. (01/00729-3)

Filed patent(s) as a result of this research project