Journal Article

Persistence of vaccine-elicited immune response up to 14 years post-HIV gp120-NefTat/AS01B vaccination

Jongert, Erik, Leroux-Roels, Isabel, Aerssens, Annelies, Yates, Nicole L., Mesia Vela, Doris, Roman, François, Tomaras, Georgia D., Sawant, Sheetal, Janssens, Michel, Van Der Meeren, Olivier, Koutsoukos, Marguerite, Leroux-Roels, Geert, Brackett, Caroline, Debois, Muriel, Seaton, Kelly E.

2020

Overview

•Long-term immune response induced by the candidate gp120-NefTat/AS01B vaccine was evaluated.•Antibodies binding to a HIV gp120 antigen panel persisted over 14 years post-vaccination.•Persistence of antibodies binding to the V1V2 scaffold was noted 2–14 years post-vaccination.•Polyfunctional gp120-specific CD4+T-cells were detected up to 14 years post-vaccination. Vaccines eliciting protective and persistent immune responses against multiple human immunodeficiency virus type 1 (HIV-1) clades are needed. This study evaluated the persistence of immune responses induced by an investigational, AS01-adjuvanted HIV-1 vaccine as long as 14 years after vaccination. This phase I, open-label, descriptive, mono-centric, extension study with a single group (NCT03368053) was conducted in adults who received ≥3 doses of the clade B gp120-NefTat/AS01B vaccine candidate 14 years earlier in a previous clinical trial (NCT00434512). Binding responses of serum antibodies targeting a panel of envelope glycoproteins, including gp120, gp140 and V1V2-scaffold antigens and representative of the antigenic diversity of HIV-1, were measured by binding antibody multiplex assay (BAMA). The gp120-specific CD4+/CD8+ T-cell responses were assessed by intracellular cytokine staining assay. At Year 14, positive IgG binding antibody responses were detected in 15 out of the 16 antigens from the BAMA V1V2 breadth panel, with positive response rates ranging from 7.1% to 60.7%. The highest response rates were observed for clade B strain V1V2 antigens, with some level of binding antibodies against clade C strains. Anti-V1V2 IgG3 response magnitude breadth, which correlated with decreased risk of infection in a previous efficacy trial, was of limited amplitude. Response rates to the antigens from the gp120 and gp140 breadth panels ranged from 7.7% to 94.1% and from 15.4% to 96.2% at Year 14, respectively. Following stimulation with gp120 peptide pool, highly polyfunctional gp120-specific CD4+ T-cells persisted up to Year 14, with high frequencies of CD40L tumor necrosis factor alpha (TNF-α), CD40L interleukin-2 (IL-2), CD40L TNF-α IL-2 and CD40L interferon gamma (IFN-γ) TNF-α IL-2 CD4+ T-cells, but no CD8+ T-cells detected. Persistent antibodies binding to HIV-1 envelope glycoproteins, including the V1V2-scaffold, and gp120-specific cellular immunity were observed in volunteers vaccinated 14 years earlier with the gp120-NefTat/AS01B vaccine candidate.

• Publisher: Elsevier Ltd
• Subject: adults / antibodies / antigenic variation / antigens / blood serum / CD4-positive T-lymphocytes / CD8-positive T-lymphocytes / cell-mediated immunity / clinical trials / glycoproteins / Human immunodeficiency virus 1 / immunoglobulin G / interferon-gamma / interleukin-2 / risk reduction / staining / tumor necrosis factor-alpha / vaccination / vaccines / volunteers