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31 The Frequency of CD8+ T-Cell Responses against the Human Immunodeficiency Virus Type 1 Gag Proteins Correlates Inversely with Plasma Viral Load
B. Edwards, A. Bansal, S. Sabbaj, M. Mulligan, and P. Goepfert*
Univ. of Alabama at Birmingham, USA
Background: Despite studies demonstrating that CD8+ T-cell responses are important in the control of HIV-1 infection, few studies have been able to correlate these responses with markers of HIV-1 disease progression.
Methods: Cell-mediated immune (CMI) responses were measured using PBMC obtained from 27 patients with chronic HIV-1 infection. The majority of the patients (85%) were not on antiretroviral therapy (ART), and the remainder had detectable plasma viral load while on therapy. CMI responses were measured using the ELISPOT assay to detect IFN-gamma-secreting PBMC after stimulation with overlapping HIV-1 peptides spanning the Gag, Pol, Env, and Nef proteins in addition to baculovirus-derived p24 and gp160 proteins.
Results: All volunteers had responses to at least 1 peptide in the HIV-1 pools (range 1-10, average 5) with all but 1 of them responding to the Gag peptide pool and 86% responding to the Pol and/or Nef peptide pools. Depletion experiments demonstrated that CD8+ T cells mediated these responses. Only 38% of the volunteers had responses to p24 and none had gp160-specific responses. Significant correlations were observed when responses to the total HIV-1 peptide pool, the Gag peptide pool, and p24 were compared with plasma viral load (PVL) (r = (0.5, p = 0.007; r = (0.60, p = 0.0008; and r = (0.42, p = 0.03 for total, Gag, and p24, respectively). Furthermore, direct correlations were observed between the absolute CD4 count and both the total peptide and Gag peptide pool responses (r = 0.46, p = 0.014; and r = 0.54, p = 0.003, respectively).
Conclusions: Gag-specific CD8+ T-cell responses correlated significantly with PVL and absolute CD4 counts using the Spearman Rank Correlation test; however, no such correlation was seen with specific T-cell responses directed toward other HIV-1 proteins. These data serve as strong evidence that the Gag protein is an essential component to be included for an optimal HIV-1 vaccine.
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