Persistence of vaccine-elicited immune response up to 14 years post-HIV gp120-NefTat/AS01 B vaccination.

Autor: Van Der Meeren O; GSK, Rixensart and Wavre, Belgium. Electronic address: olivier.x.van-der-meeren@gsk.com., Jongert E; GSK, Rixensart and Wavre, Belgium., Seaton KE; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, United States; Department of Surgery, Duke University, Durham, NC 27710, United States., Koutsoukos M; GSK, Rixensart and Wavre, Belgium., Aerssens A; Center for Vaccinology, Ghent University and Ghent University Hospital, Ghent, Belgium., Brackett C; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, United States; Department of Surgery, Duke University, Durham, NC 27710, United States., Debois M; GSK, Rixensart and Wavre, Belgium., Janssens M; GSK, Rixensart and Wavre, Belgium., Leroux-Roels G; Center for Vaccinology, Ghent University and Ghent University Hospital, Ghent, Belgium., Mesia Vela D; GSK, Rixensart and Wavre, Belgium., Sawant S; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, United States; Department of Surgery, Duke University, Durham, NC 27710, United States., Yates NL; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, United States; Department of Surgery, Duke University, Durham, NC 27710, United States., Tomaras GD; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, United States; Department of Surgery, Duke University, Durham, NC 27710, United States; Department of Immunology, Duke University, Durham, NC 27710, United States; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, United States., Leroux-Roels I; Center for Vaccinology, Ghent University and Ghent University Hospital, Ghent, Belgium., Roman F; GSK, Rixensart and Wavre, Belgium.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2020 Feb 11; Vol. 38 (7), pp. 1678-1689. Date of Electronic Publication: 2020 Jan 10.
DOI: 10.1016/j.vaccine.2019.12.058
Abstrakt: 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/AS01 B 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/AS01 B vaccine candidate.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [O.V.D.M, E.J., M.K., M.D., M.J., D.M.V. and F.R. are employed by the GSK group of companies. O.V.D.M, E.J., M.K., D.M.V. and F.R. also hold shares from the GSK group of companies. M.K. also reports receiving a grant from the European Commision for the EbolaVac program outside of the submitted work. K.S., C.B., S.S., G.D.T. received financial and other support without any personal financial benefit from the GSK group of companies for the conduct of the study. They also report grants from the GSK group of companies to their institution outside of the submitted work. A.A., G.LR. and I.LR report grant from the GSK group of companies to their institutions (Ghent University Hospital and Ghent University) to compensate the costs for the conduct of the study. I. LR. also reports grant from the GSK group of companies to her institutions (Ghent University Hospital and Ghent University) to finance the conduct of other vaccine trials. N.L.Y. has nothing to disclose.].
(Copyright © 2020 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE