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67 Humoral Anti-Tat Immune Response in Individuals Infected with Different HIV-1 Clades Correlates with the Asymptomatic Stage of HIV-1 Infection and with Nonprogression to AIDS
F. Ensoli1, V. Fiorelli2, S. Buttò*2, A. Tripiciano2, A. Scoglio2, M. J. Ruiz-Alvarez2, B. Collacchi1, A. Caputo3, T. Wagner2, M. Colvin4, E. Vardas5, A. Cafaro2, F. Aiuti1, G. Rezza2, B. Ensoli2, and the Tat Multicentric Study Grp.
1Univ. of Rome “La Sapienza,” Italy; 2Inst. Superiore di Sanità, Rome, Italy; 3Univ. of Ferrara, Italy; 4Med. Res. Council, Durban, South Africa; and 5Chris Hani Baragwanath Hosp., Johannesburg, South Africa
Background: To determine prevalence, cross-recognition, and correlation with disease progression of the immune response to Tat in distinct human populations infected by different HIV-1 clades.
Methods: Sera from 501 HIV-1-infected individuals from Italy, Uganda, and South Africa were tested for anti-Tat antibodies by ELISA using a highly purified, biologically active Tat protein (BH10 clone, clade B). Ninety-seven Italian patients in stage A, stratified by anti-Tat serology, were investigated longitudinally. Tat-specific B-cell epitopes were identified by overlapping peptides.
Results: Anti-Tat IgG and IgM were found in 13.2 and 6.9% Italian patients, respectively, and were significantly associated with the asymptomatic status of infection. Longitudinal analysis showed that patients in stage A lacking anti-Tat IgG were more likely to progress to disease. A major B-cell epitope was defined within the amino-terminal domain of Tat (aa 1(20). Similar prevalence of anti-Tat antibodies was found in individuals from Uganda (10.8%) and South Africa (18.3%) infected by different HIV-1 clades (A, B, C, and D). Epitope mapping confirmed the amino-terminal region as a major B-cell epitope.
Conclusions: The presence of anti-Tat antibodies significantly correlates with the asymptomatic stages of infection and with a reduced risk of disease progression. Anti-Tat antibodies elicited by different HIV-1 clades cross-react with the clade B Tat suggesting that the immune response elicited by a vaccine based on a biologically active, clade B Tat protein might control the infection by different HIV-1 subtypes.
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