In addition to their direct antiviral effect, broadly neutralizing antibodies (bNAbs) against HIV-1 may have a vaccinal effect by stimulating T cell-specific immunity via immune complex formation leading to dendritic cell activation and enhanced antigen processing and presentation. This effect has been shown to increase the chance of post-treatment control in SHIV-infected non-human primates. To determine whether a vaccinal effect also occurs in humans, we measured HIV-1-specific T cell immune responses in newly diagnosed HIV-1-infected individuals starting antiretroviral therapy (ART) with or without the potent bNAb 3BNC117.
Cryopreserved PBMCs were obtained from the eCLEAR study (NCT03041012) in which HIV-1-infected individuals starting ART were randomized to receive: 1) ART alone, 2) ART+3BNC117 at day 7 and 21 after ART initiation, 3) ART+romidepsin (RMD) at day 10, 17 and 24 after ART initiation or 4) ART+3BNC117+RMD. We used the activation-induced marker (AIM) assay to quantify HIV-1-specific T cell immune responses pre-ART, at 3 months and 12 months after ART initiation. HIV-1-specific CD4+ or CD8+ T cells were defined as PD-L1+4-1BB+, PD-L1+CD69+, CD69+4-1BB+ or PD-L1+4-1BB+CD69+ following peptide pool stimulations against either HIV-1 Env, Gag, Nef or Pol.
At ART initiation, all 4 groups had comparable levels of HIV-1-specific CD4+ and CD8+ T cells responses towards HIV-1 Env, Gag, Nef and Pol; as expected, the pool of HIV-1-specific cells within the total CD8+ compartment contracted following ART initiation to 12 months into ART (median frequency of 2.67% vs 0.79%, p=0.01) while the CD4+ compartment were more sustained over time (median frequency of 1.86% vs 1.30% , p=0.33). However, the frequency of Gag-specific CD8+ T cells was significantly higher in individuals that received 3BNC117 (with or without RMD) at 3 months after starting ART compared to ART control group (median 0.69% vs 0.29%, respectively, p=0.04) and at 12 months of ART (median 0.91% vs 0.31% respectively, p=0.03).
Our results suggest that bNAb therapy at the time of ART initiation may have a vaccinal effect by inducing long-lasting Gag-specific T CD8+ cells responses, which have been associated with immune mediated virus control.