CD8 + T-cell Mediated HIV Inhibition after Vaccination with a DNA/Recombinant Ad5 (rAd5) HIV Vaccine Is Similar to that Seen in Treated HIV Infection

PD03.01 LB

Background: HVTN 505, a phase 2b trial assessing if a DNA/rAd5 HIV vaccine prime/boost regimen reduces HIV acquisition or viremia post infection, halted vaccinations in 2013 due to efficacy futility, though it induced substantial CD8⁺ T-cell responses. We examined whether vaccine-induced T cells in HVTN 505 were unable to inhibit virus replication, as a potential reason for their inability to control viremia post infection.

Methods: CD8⁺ T cells from 48 participants (38 vaccine, 10 placebo) were tested pre-immunization and at peak immunogenicity (4 weeks post rAd5 boost) for their ability to inhibit HIV-1 replication in autologous CD4⁺ T cells infected with a NanoLuc^®-secreting JR-CSF infectious molecular clone. Relative light units (RLU) were measured at day 7, Δlog inhibition of virus (difference of log RLU in the presence vs. absence of CD8⁺ T cells) is reported for an effector:target ratio of 5:1. Responses were considered positive if above the mean + 3SD of baseline and placebo samples (1.05 log). Seven subjects with chronic HIV infection on antiretroviral treatment (ART) served as controls.

Results: Viral inhibition by CD8⁺ T cells was significantly greater in vaccinees at peak immunogenicity than pre-immunization (p < 0.0001); no changes over time were observed in placebo recipients (p = 0.7). The response rate was 61%, with median Δlog inhibition of 1.9 logs (range 1.2–2.6) in responders. This level of inhibition is similar to that in HIV-infected subjects requiring ART to control viremia (median 2.1 logs, range 1.7–2.8; p = 0.06).

Conclusions: The DNA/rAd5 vaccine in HVTN 505 led to significant induction of CD8⁺ T-cell responses able to inhibit HIV-1 replication in vitro, but the magnitude in responders was comparable to that observed in treated HIV infected subjects requiring ART to control viremia. It is thus likely that vaccination must elicit responses of higher magnitude (such as those observed in elite HIV controllers in similar assays) to drive an overall reduction in viral load post infection.