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5th International AIDS Society Conference on HIV Pathogenesis and TreatmentCape Town - July 19 - 22, 2009 |
HLA-RESTRICTED EPITOPES FROM AUTOLOGOUS SEQUENCES AS A TOOL TO CHARACTERIZE THE ACTUAL BREADTH OF IMMUNE RESPONSES IN ELITE CONTROLLERS
IAS Conf HIV Pathog Treat 2009 Jul 19-22;5th: Abstract No. MOAA103
L.F. Tarosso1
, M.M. Sauer2, H. Tomiyama2, S. Sanabani3, E.C. Sabino3, J. Sidney4, A. Sette4, D.I. Watkins5, E.G. Kallas1,2
1University of Sao Paulo, Clinical Immunology and Allergy Division, Sao Paulo, Brazil, 2Federal University of Sao Paulo,
Division of Infectious Diseases, Sao Paulo, Brazil, 3Sao Paulo Blood Bank, Sao Paulo, Brazil, 4La Jolla Institute for Allergy
and Immunology, La Jolla, United States, 5University of Wisconsin-Madison, Wisconsin Regional Primate Center,
Madison, United States
BACKGROUND: The capacity of some HIV-infected subjects, termed elite controllers (ECs), to mantain undetectable plasma viral loads without antiretroviral drugs provides hope for vaccine strategies designed to induce a controller phenotype and prevent disease progression. Immune responses against HIV are normally studied using HIV-1 consensus B 15-mers that overlap by 11 amino acids. Unfortunately, this method may underestimate the real breadth of the cellular immune responses against the autologous sequence of the infecting virus.
METHODS: Here we describe HLA-restricted CTL-responses against Nef and Vif peptides synthesized from HIV-1 consensus B and the autologous sequences in six ECs assessed by ELISpot-IFN-γ. A response was considered positive if the number of SFUs exceeded 55 SFU per 106 cells and was at least four-fold the level of the sample with no peptide.RESULTS: Most of the patients (four out of six) had broader immune responses against minimal optimal HLA-restricted epitopes than the responses against to the Consensus B 15-mer non-HLA-restricted peptides. The number of HLA-restricted epitopes recognized was 13 for Vif and 20 for Nef. Using 15-mer non-HLA-restricted epitopes, the number was five and 13 for Vif and Nef peptides, respectively. Also the mean number of spots detected using the HLA-restricted approach was higher (9,185 SFU per 106 cells for Vif and 14,255 SFU per 106 cells for Nef epitopes) when compared with the 15-mer assays (2,665 SFU per 106 cells for Vif and 6,445 SFU per 106 cells for Nef peptides).
CONCLUSIONS: These findings suggest that immune responses assessed using 15-mer overlap by 11 aminoacids may underrepresent the real breadth of immune control of the infecting virus and that the knowledge about succesful responses in ECs could be improved reviewing the methods employed.
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2009-07-22
MOAA103
Oral Abstract Session: MOAA1 - Control of HIV by Cellular Immunity
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