AEGiS-14IAC: HIV-1 regulatory proteins (Nef, Tat, Rev, Vif, Vpu, Vpr)-CTL responses and epitope mapping in subtype A/E infected Thais with CD4>300 cells/mm<sup><font size="1" class="small">3</font></sup>.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

HIV-1 regulatory proteins (Nef, Tat, Rev, Vif, Vpu, Vpr)-CTL responses and epitope mapping in subtype A/E infected Thais with CD4>300 cells/mm³.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10021)

Buranapraditkun S, Ruxrungtham K, Sirivichayakul S, Kosonsiriluk S, Kerdsanti S, Hansasuta P, Rowland-Jones S, Warachit P, Phanuphak P
Chulalongkorn University, Bangkok, Thailand

BACKGROUND: There are no data on CTL responses against subtype A/E HIV-1 regulatory proteins. In addition, the HLA polymorphism among Thais is also remarkably different from the western cohorts. Our previous studies had identified a common new HLA C1 restricted subtype A/E gag epitope. Thus, CTL studies against HIV-1 subtype A/E regulatory proteins in Thailand is warranted.

METHOD: CTL responses and epitope mapping and HLA restriction were performed by IFN-γ ELISPOT assay. HIV-1 subtype A/E truncated peptides of Nef, Tat, Rev, Vif, Vpu, Vpr (15-21 a.a in length, with 10-a.a overlaps between sequential peptides) were used for CTL screening (16 pools of peptides) and epitope mapping. HLA class I and HIV-1subtype was analyzed by genotyping. The positive cut-off of ELISPOT was 60 SFU/106 PBMCs and 2 folds higher than the background.

RESULTS: 18 subtype A/E infected and treatment naïve patients were included. Mean CD4 count 515 cells/mm³. HLA typing showed: A11 (50%), A24 (28%), A2 (31%); B40, B58, B15 (25%), B27, B46 (19%); and C7 (50%), C3, C1 (13%) and C6 (25%). All patients showed ELISPOT positive against at least one pool of the peptides. The proportion of positive responses to Nef, Vpr, Tat, Rev, Vif, Vpu was 94, 50, 44, 28, 17, and 17 % respectively. CTL epitope mapping was performed in 3 patients. Eleven epitopes were identified (4 in Nef, 2 in each of Rev, Vif, Vpr; and 1 in Tat). Interestingly, among those 5 possibly novel epitopes are identified.

DISCUSSION: IFN-γ ELISPOT-based CTL responses to HIV-1 regulatory proteins (94% nef and 50% vpr) are common among subtype A/E HIV-1 infected Thais. The results support the potentially role of HIV-1 regulatory proteins which should be included in an candidate vaccine. Further characterization of those possibly novel epitopes is under way.

Keywords: AEGIS, HIV-1, Antigens, CD4, Epitopes, HIV Infections, Epitope Mapping, HIV Seropositivity, Thailand, Human, immunology

020707
A10021