HIV-1 TAT-specific CTL responses in untreated HIV-1 infected patients with CD4+T cell>=300 cells/microlitre

Abstract

Circulating recombinant form AE is the most common HIV-1 subtype causes AIDS epidemic in Thailand. It is different from molecular sequence subtype B commonly found in developed countries. Cytotoxic T lymphocytes (CTLs) are considered as an important protective immunity against HIV infection. There are no data on CTL responses against HIV-1 CRF01_AE trans activator of transcription or Tat protein that is one of the good candidates for vaccine design. The ident cation of common and/ or novel Tat-specific CTL responses and epitope mapping may provide some specific and additional useful data for the research and development of CRF01_AE Tat-based vaccine. This study is to find Tat-specific CTL responses and epitope mapping in 20 untreated HIV-1 infected Thais by using gamma-interferon (IFN-y) enzyme-linked immunospot (Elispot) assay. HIV-1 CRF01_AE based truncated Tat peptides 17-21 amino acids in length, and overlapped by 10 amino acids were used for the study. Tat specific CTL responses were screened using 2 pools of peptides, each contains 5 truncated Tat peptides. The positive cut-off of Elispot was defined after background subtracted as ≥100 spot forming units (SFU) / 106 PBMCs and 2 folds higher than negative control. Patients who showed positive results were then further identified for Tat specific epitope (s). Ten out of 20 patients (50%) showed IFN- γ -Elispot positive to pooled Tat peptides. The magnitude of responses ranged from 260-912 SFU/106 PBMCs (Median 498 SFU/106 PBMCs). Seven patients who showed positive results to the pooled peptides showed IFN- γ-Elispot positive to individual peptides. The magnitude of responses ranged from 128-1,264 SFU/106 PBMCs (Median = 460). Six epitopes were identified and at least one may be a novel epitope. Tat has been targeted recently in a vaccine strategy to confine virus replication and transmission and to block or retard progression to AIDS. However, this study found similar to previously reported in the subtype c study that only one-third (35%) of HIV-1 infected individuals showed Tat-specific IFN-y responses. Whereas other studies including our group had shown that gag- and pol-specific CTL responses much more common (80% or more). Thus, Tat may consider as a good candidate to be included in HIV vaccine design rather to Tat vaccine.