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Vaccine antigens modulate the innate response of monocytes to Al(OH)3.
Kooijman, Sietske; Brummelman, Jolanda; van Els, Cécile A C M; Marino, Fabio; Heck, Albert J R; van Riet, Elly; Metz, Bernard; Kersten, Gideon F A; Pennings, Jeroen L A; Meiring, Hugo D.
Afiliação
  • Kooijman S; Intravacc, Bilthoven, The Netherlands.
  • Brummelman J; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Science Faculty, Utrecht University, Utrecht, The Netherlands.
  • van Els CACM; Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
  • Marino F; Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
  • Heck AJR; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Science Faculty, Utrecht University, Utrecht, The Netherlands.
  • van Riet E; Netherlands Proteomics Centre, Utrecht, The Netherlands.
  • Metz B; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Science Faculty, Utrecht University, Utrecht, The Netherlands.
  • Kersten GFA; Netherlands Proteomics Centre, Utrecht, The Netherlands.
  • Pennings JLA; Intravacc, Bilthoven, The Netherlands.
  • Meiring HD; Intravacc, Bilthoven, The Netherlands.
PLoS One ; 13(5): e0197885, 2018.
Article em En | MEDLINE | ID: mdl-29813132
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Monócitos / Vacinas contra Difteria, Tétano e Coqueluche Acelular / Hidróxido de Alumínio / Imunidade Inata / Antígenos de Bactérias Limite: Adult / Humans Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Monócitos / Vacinas contra Difteria, Tétano e Coqueluche Acelular / Hidróxido de Alumínio / Imunidade Inata / Antígenos de Bactérias Limite: Adult / Humans Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Holanda