P26.07
Background: CD8 T-cells suppress HIV replication and this activity controls acute viremia and slows progression to AIDS. We have validated a functional ex vivo Viral Inhibition Assay (VIA) to measure virus suppression in HIV vaccine recipients.
Methods: VIA, using a panel of 8 subtype A to D viruses, was compared in 45 vaccine recipients from two prime-boost trials: B002 trial assessed adjuvanted Gag-Pol-Nef Fusion Protein (F4/AS01) co- or sequentially administered with replication-defective Ad35 vector encoding clade A genes gag, RT, integrase, nef (Ad35-GRIN). B004 trial assessed plasmid DNA (HIVMAG) encoding clade B gag-pol, env, nef-tat-vif, administered by intramuscular electroporation alone or with pDNA IL-12 and Ad35-GRIN and Ad35-Env. VIA assessed by the log reduction in HIV p24 production was measured at baseline, and 4 weeks after prime and boost immunizations.
Results: VIA activity was detected in 13/19 vaccines (68%) after priming with 3 HIVMAG+/−IL-12, and after 2 F4/AS01 administrations in 2/8 (25%) vaccines. After Ad35-GRIN+/− Env boost, VIA activity was detected in 18/19 (95%) and 6/8 (75%) volunteers respectively. When F4/AS01 was co-administered with Ad35-GRIN, VIA was detected in 5/8 vaccines (63%) after the 1st and 7/9 (78%) after the 2nd and 3rd administrations. Clade B (IIIB) and A (U455) viruses were inhibited most frequently. In both trials, at 4 weeks after Ad-HIV vaccine, VIA activity was similar in magnitude and in breadth, assessed by the number of viruses inhibited. The mean log inhibition for responders was 2.7 (range 1.5–4.8) and an average of 3 viruses were inhibited after Ad35-GRIN+/−Ad35-Env. VIA from these 2 trials will be compared with VIA induced by other vaccines and regimens.
Conclusions: Modest frequency and magnitude VIA response to electroporated HIVMAG or F4/AS01 was significantly boosted by combination with Ad35-GRIN+/−Ad35-Env. Thus Ad35 provides a suitable platform for induction of functional CD8-T cells with breadth and potency.
