Vaccine antigens modulate the innate response of monocytes to Al(OH)3

PLoS One. 2018 May 29;13(5):e0197885. doi: 10.1371/journal.pone.0197885. eCollection 2018.

Abstract

Aluminum-based adjuvants have widely been used in human vaccines since 1926. In the absence of antigens, aluminum-based adjuvants can initiate the inflammatory preparedness of innate cells, yet the impact of antigens on this response has not been investigated so far. In this study, we address the modulating effect of vaccine antigens on the monocyte-derived innate response by comparing processes initiated by Al(OH)3 and by Infanrix, an Al(OH)3-adjuvanted trivalent combination vaccine (DTaP), containing diphtheria toxoid (D), tetanus toxoid (T) and acellular pertussis (aP) vaccine antigens. A systems-wide analysis of stimulated monocytes was performed in which full proteome analysis was combined with targeted transcriptome analysis and cytokine analysis. This comprehensive study revealed four major differences in the monocyte response, between plain Al(OH)3 and DTaP stimulation conditions: (I) DTaP increased the anti-inflammatory cytokine IL-10, whereas Al(OH)3 did not; (II) Al(OH)3 increased the gene expression of IFNγ, IL-2 and IL-17a in contrast to the limited induction or even downregulation by DTaP; (III) increased expression of type I interferons-induced proteins was not observed upon DTaP stimulation, but was observed upon Al(OH)3 stimulation; (IV) opposing regulation of protein localization pathways was observed for Al(OH)3 and DTaP stimulation, related to the induction of exocytosis by Al(OH)3 alone. This study highlights that vaccine antigens can antagonize Al(OH)3-induced programming of the innate immune responses at the monocyte level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aluminum Hydroxide / pharmacology*
  • Antigen Presentation / drug effects
  • Antigens, Bacterial / immunology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / immunology*
  • Humans
  • Immunity, Innate / drug effects*
  • Immunity, Innate / immunology*
  • Inflammasomes / metabolism
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Monocytes / cytology
  • Monocytes / drug effects*
  • Monocytes / immunology*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology

Substances

  • Antigens, Bacterial
  • Diphtheria-Tetanus-acellular Pertussis Vaccines
  • Inflammasomes
  • Interleukin-10
  • Aluminum Hydroxide
  • Interferon-gamma

Grant support

SK is funded by a strategic research grant (SOR) of the Ministry of Health and Welfare, The Netherlands (AS200107). The Ministry of Health and Welfare funded the project and the salary of SK but the Ministry did not have any role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section. This work was also partly supported by the Proteins@Work, a 628 program of the Netherlands Proteomics Centre financed by the Netherlands Organisation for Scientific Research (NWO) as part of the National Roadmap Large-scale Research Facilities of the Netherlands (project number 184.032.201). Proteins@Work funded the salary of FM but did not have a role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.