AEGiS-13IAC: Cross-Clade HIV specific CTL study and CTL epitope mapping in clade E/A HIV-Infected thais.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Cross-Clade HIV specific CTL study and CTL epitope mapping in clade E/A HIV-Infected thais.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrA595)

Buranapraditkun S, Ruxrungtham K, Warachit P, Honda M, Phanuphak P
S. Buranapraditkun, Chulalongkorn University, Faculty of Medicine, Department of Medicine, Chulalongkorn University, Bangkok10330, Thailand, Tel.: +66-2-254-2323, Fax: +66-2-254-7577, E-mail: bsuprane@chula.ac.th

BACKGROUND: There are 2 clades of HIV-1: E/A and B (B'>B) found in Thailand. Cross-clade CTL study and epitope mapping are warranted for HIV vaccine development to be tested in Thailand.

OBJECTIVES: To find the prevalence of cross-clade CTL activities in HIV-infected Thais with CD4+ >300 cell/ul. And to identify common and/or novel HIV-1 CTL gag epitopes.

METHODS: Classic Cr51 release CTL assays were performed in 22 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 (aa 1-499, consensus sequence of 92UG037, each is 20 aa in length, with 10-aa overlaps between sequential peptides) were used for gag-CTL epitope mapping. . The plasma samples were serotyped for HIV-1 subtypes.

RESULTS: Mean CD4+ cell counts 528 cells/ul, median plasma HIV-RNA 6510 copies/ml (range >50-52,935). From serotyping, 10 patients were infected with clade E, the rest awaits for further genotyping. All the patients showed CTL activity against clade A gag and pol (10/10, 100%), whereas 80 % and 30% revealed cross-reactive CTL against clade B gag and pol, respectively. There are 6 epitopes identified in 3 evaluated patients. Four epitopes locate in p24 region and 2 in p17 region. Based on the Los Alamos HIV immunology database, 4 of them are restricted by HLA B8, A2, and A26. However, there are 2 epitopes that requires further HLA restriction study. Discussions: In HIV vaccine design for CTL induction, the breadth of cross clade reactivity needs to be considered. Our results indicate that HIV clade A-gag provided much higher CTL cross-reactivity than HIV clade A-pol. Thus, HIV-1 gag clade A is suitable to be included in a candidate HIV vaccine to be evaluated in Thailand.

Keywords: AEGIS, HIV Infections, HIV-1, HIV Seropositivity, Epitopes, Epitopes, T-Lymphocyte, Epitope Mapping, AIDS Vaccines, CD4 Lymphocyte Count, Thailand, Human, immunology
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