Background
Therapeutic HIV vaccines aim to elicit T cell responses, but humoral responses are also relevant for viral control. Here we report binding and neutralizing antibody responses in a randomized controlled trial (RCT) of a DNA vaccine with or without envelope (PENNVAX; NCT03606213).
Methods
Two studies were conducted: a randomized study in participants who started antiretroviral therapy (ART) in chronic HIV and a single-arm study in those who started ART early. Vaccines contained multiclade (A, B, C, D) consensus Gag and Pol plasmids with or without two Env plasmids (clades A, C). Chronic cohort participants were randomized to placebo (PBO; N=15), Gag/Pol/IL-12 DNA (GP; N=14), or Gag/Pol/Env/IL-12 DNA (GPE; N=16). The early cohort (N=11) received Gag/Pol/Env/IL-12 DNA (GPE-E). Plasma Gag- and Env-specific IgG binding antibodies (bAbs) were measured by Luminex at baseline (B1), week 14 (W14, 2 weeks post-vaccination), and week 48 (W48). Neutralizing antibodies (nAbs) against three Tier 1, six Tier 2, and autologous (PBMC and dQVOA-derived) viruses were measured by Labcorp-Monogram Biosciences PhenoSense Monoclonal Antibody Assay using B1 and W14 purified plasma IgG. Comparisons were by Wilcoxon tests.
Results
Env- but not Gag-specific bAbs were lower at baseline in the early vs chronic cohort (p<0.01), as was Tier 1 nAb breadth (median 1 vs 3 viruses, p<0.001), without difference in Tier 2 breadth. Autologous nAbs (anAbs) were detected in only 20 (44%) chronic and 3 (27%) early cohort participants. Gag-specific bAbs increased significantly from B1 to W14 and B1 to W48 in the GP arm (within-arm p<0.01 for both and p=0.04 for both compared to PBO) but not GPE or GPE-E arms. No change in Env-specific bAb was observed with GPE vaccination in the chronic cohort, but gp120 bAb were significantly boosted in the early cohort from B1 to W14 and B1 to W48 (within-arm p<0.01 for both). Tier 1/2 neutralization breadth increased with vaccination in 7/16 (44%) GPE, 3/14 (21%) GP, and 1/15 (7%) PBO participants, but the magnitude of Tier 1, Tier 2, and anAb responses did not significantly change in any arm.
Conclusions
We show that Env-containing DNA vaccine may modestly boost or broaden Env binding and heterologous nAb responses, but impairs simultaneous boosting of Gag-specific antibodies. These findings mirror previously shown Gag-specific T-cell responses in this RCT. Autologous neutralizing responses were detected in only a subset of participants and not boosted by vaccination.
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