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66 Cell-Mediated Cross-Clade Immune Reactivity among Ethiopian Emigrants Infected with Clade C HIV-1
G. Ferrari*1, L. Earhart1, J. Currier2, L. Jagodzinski2, J. Cox2, S. Osmanov3, D. Birx2, K. Weinhold1, and S. Maayan4
1Duke Univ., Durham, NC; 2The US Military HIV Res. Prgm., Rockville, MD; 3WHO/UNAIDS, Geneva, Switzerland; and 4Hadassah Univ. Hosp., Jerusalem, Israel
Background: To define highly conserved regions in the Gag protein that may elicit cross-clade cell-mediated immunity, we studied a cohort of HIV clade-C-infected Ethiopian emigrants to Israel.
Methods: A cohort of 15 HIV seropositive individuals was studied. Virus load was determined by the NASBA method and confirmed by ROCHE Amplicor v.1.5. The HLA haplotype was characterized by high resolution molecular. The anti-Gag cell-mediated immune response was studied by an interferon-gamma ELISpot assay using pools of five 20-mer peptides, overlapping by 10 aa, whose sequences were based on the clade B HXB2 and clade C 96ZM651.8 isolates.
Results: In 11 patients, an equal or greater number of clade C peptide pools was recognized compared with clade B pools. Cross-clade recognition was not detectable in patient 17, who had a low CD4 count (40 cells/ml), a low virus load (2,500 copies/ml), and no anti-retroviral therapy at the time of study. Patient 11 recognized neither clade B nor clade C sequences, despite a high CD4 count (639 cells/ml) and relatively low virus load (2,400 copies/ml). The highest levels and percentage of reactivities (i.e., (50%) were detected against HIV-1 p17 (aa 1(110). Reactivity against the p24 region was unexpected since clade B p24 sequences (aa 200(360) were recognized in more than 50% of the subjects and more frequently than clade C sequences. Only 2 patients out of 7 showed good reactivities against the p15 region aa 399(458 (SFC > 100 cells/106). HLA class I allelic frequencies were found to more closely resemble those of a Caucasoid population.
Conclusions: The p17 protein appears to be the most recognized antigenic region among a clade C-infected Ethiopian cohort of emigrants to Israel, with HLA class I allelic frequencies different from the sub-Saharan populations. This type of information may be useful in developing a worldwide efficacious HIV vaccine.
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