Dendritic cell immunotherapy followed by cART interruption during HIV-1 infection induces plasma protein markers of cellular immunity and neutrophil recruitment

PLoS One. 2018 Feb 1;13(2):e0192278. doi: 10.1371/journal.pone.0192278. eCollection 2018.

Abstract

Objectives: To characterize the host response to dendritic cell-based immunotherapy and subsequent combined antiretroviral therapy (cART) interruption in HIV-1-infected individuals at the plasma protein level.

Design: An autologous dendritic cell (DC) therapeutic vaccine was administered to HIV-infected individuals, stable on cART. The effect of vaccination was evaluated at the plasma protein level during the period preceding cART interruption, during analytical therapy interruption and at viral reactivation. Healthy controls and post-exposure prophylactically treated healthy individuals were included as controls.

Methods: Plasma marker ('analyte') levels including cytokines, chemokines, growth factors, and hormones were measured in trial participants and control plasma samples using a multiplex immunoassay. Analyte levels were analysed using principle component analysis, cluster analysis and limma. Blood neutrophil counts were analysed using linear regression.

Results: Plasma analyte levels of HIV-infected individuals are markedly different from those of healthy controls and HIV-negative individuals receiving post-exposure prophylaxis. Viral reactivation following cART interruption also affects multiple analytes, but cART interruption itself only has only a minor effect. We find that Thyroxine-Binding Globulin (TBG) levels and late-stage neutrophil numbers correlate with the time off cART after DC vaccination. Furthermore, analysis shows that cART alters several regulators of blood glucose levels, including C-peptide, chromogranin-A and leptin. HIV reactivation is associated with the upregulation of CXCR3 ligands.

Conclusions: Chronic HIV infection leads to a change in multiple plasma analyte levels, as does virus reactivation after cART interruption. Furthermore, we find evidence for the involvement of TBG and neutrophils in the response to DC-vaccination in the setting of HIV-infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Case-Control Studies
  • Dendritic Cells / immunology*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / therapy*
  • HIV-1 / physiology
  • Humans
  • Immunity, Cellular*
  • Insulin Resistance
  • Male
  • Neutrophils / immunology*
  • Receptors, CXCR3 / metabolism
  • Virus Replication

Substances

  • Anti-HIV Agents
  • CXCR3 protein, human
  • Receptors, CXCR3

Grant support

This work was supported by the VIRGO consortium that is funded by the Dutch government project number FES0908. JT was also supported through grants awarded to Psynova Neurotech Ltd. by the European Union FP7 funding scheme: Marie Curie Actions Industry Academia Partnerships and Pathways (ref. 286334, PSYCH-AID project); and by the Dutch Fund for Economic Structure Reinforcement, the NeuroBasic PharmaPhenomics project (ref. 0908). SB was also supported by a grant from the Stanley Medical Research Institute (SMRI). JLA was supported by the Wetenschappelijk Fonds Willy Gepts of the UZ Brussel. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.