Abstract:
There are 2 clades of HIV-1: A/E and B (B’ is more common than B) found in Thailand. It is now believed that an effective vaccine should be able to generate broad cross-clade CTL responses. Cross-clade CTL study and epitope mapping are therefore warranted for HIV vaccine development to be tested in Thailand. This study is to find the prevalence of cross-clade CTL activities against HIV-1 gag and pol in HIV-1- infected Thai patients with CD4+ ≥ 300 cells/cu.mm. and to identify common and/or novel HIV-1 CTL gag epitopes. Classic Cr51 release CTL assays were performed in 25 HIV-1 infected Thai patients. Recombinant HIV-1 gag and pol vaccinia for both clade A and B were used. HIV-1 clade A gag truncated peptides amino acid 1-499, consensus sequence of 92UG037, each is 20 amino acids in length, with 10 amino acids overlaps between sequential peptides were used for gag CTL epitope mapping. Dried pack cell samples were tested genotypically for HIV-1 subtypes. Mean CD4+ T cell counts 540 ± 179 cells/cu.mm (range 307-978), median plasma HIV-RNA 6936 copies/ml (range 886-57022). From genotyping, 23 patients found infected with HIV-1 clade A/E, 2 patients were clade B infection. All of the patients showed CTL activity against clade A gag (100%) and 21/25 (84%) against pol A, whereas 16/25 (64%) and 5/25 (20%) showed CTL against clade B gag and pol, respectively. In HIV-1 clade A/E infected 23 patients, HIV-1 gag region showed the highest cross-clade CTL activity (14/23, 61%), but only 22% (5/23) showed cross-clade CTL activity against pol region. There are 18 epitopes identified in 19 evaluated HIV-1 clade A/E patients. Seven epitopes locate in pl 7, 10 in p24 and 1 in p6 regions. In the HLA class I-restriction study, 3 patients were analyzed. Three epitopes were found to be restricted by HLA A2, B7 and Cwl. A new HLA Cwl restricted p24 CTL epitope, i.e. gag A residues 271-290: NKIVRMYSPVSIL DIKQGPK was detected. Three potential CTL epitopes were also identified and need further investigation. In conclusion, HIV-1 gag is the most common target of CTL responses among HIV-1 infected Thais. In addition, cross-clade CTL activity against gag is 3 folds higher than to pol. Thus, HIV-1 gag clade A is suitable to be included in a candidate HIV vaccine to be evaluated in Thailand.
