CD8+ T cell inhibitory activity and targeting of beneficial regions and conserved elements within the HIV proteome.

<p>CD8+ T cell responses to peptides based on (<b>A</b>) clade-specific ‘beneficial’ regions and (<b>B</b>) Gag ‘conserved elements’ were measured by IFN-γ Elispot assays. Net responses (background subtracted) are shown; values for negative controls were median (IQR)– 10 (0–15) SFU/million CD8+ T cells. Horizontal lines indicate median values. HVTN vaccinees and placebos are shown as closed and open symbols respectively in <b>A</b>. In <b>B</b>, HVTN subjects are grouped together and represented as follows: HVTN 502—vaccinees, black closed circles, placebos, black open circles; HVTN 503—vaccinees, grey closed circles, placebos, grey open circles. VC are shown as triangles in <b>A & B</b>. Six HVTN 503 subjects were excluded as viral subtype data were not confirmed at the time of the analysis. One VC subject was excluded as no sample was available for Elispot assay. <b>C.</b> Correlation between CD8+ T cell inhibition of a clade-matched virus (CD8+/CD4+ cell ratio = 2:1) and magnitude of CD8+ T cell responses to beneficial peptides (summed) in 26 HVTN subjects. <b>D.</b> The analysis was repeated after removal of subjects with protective HLA class I alleles and (<b>E</b>) with short-term cell lines expanded from CD8+ T cells recovered from Elispot assays in 15 subjects that were then tested with individual peptides from the pools which elicited a response in the ex vivo Elispot assay. <b>For C-F</b>: closed circles—502 and 503 vaccinees; open circles—502 and 503 placebos. <b>F.</b> Correlation between CD8+ T cell inhibition (2:1 ratio) of a clade-matched virus and magnitude of CD8+ T cell responses to conserved elements peptides in 27 HVTN subjects (left panel—sum of all CE peptides, middle—CE pool A, right—CE pool B).