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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Olivier Van Der Meeren, Erik Jongert, Kelly E Seaton, Marguerite Koutsoukos, Annelies Aerssens, Caroline Brackett, Muriel Debois, Michel Janssens, Geert Leroux-Roels, Doris Mesia Vela, Sheetal Sawant, Nicole L Yates, Georgia D Tomaras, Isabel Leroux-Roels, François Roman
• Journal: Vaccine (Vaccine) Vol. 38 Issue 7 Pg. 1678-1689 (02 11 2020) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 31932137 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• AIDS Vaccines
• HIV Antibodies
• HIV Envelope Protein gp120

Topics

• AIDS Vaccines (immunology)
• Adult
• Antibody Formation
• HIV Antibodies (blood)
• HIV Envelope Protein gp120 (immunology)
• HIV Infections (prevention & control)
• HIV-1
• Humans
• Immunity, Cellular
• Vaccination