title: The TLR-specific adjuvants R-848 and CpG-B endorse the immunological reaction of neonatal antigen-presenting cells.
abstract: Preterm neonates display an impaired vaccine response. Neonatal antigen-presenting cells (APCs) are less effective to induce an adaptive immune response and to promote the development of immunological memory. Efficient adjuvantal toll-like receptor (TLR)-triggering may overcome the neonatal immunological impairment. Accordingly, the aim of this study was to investigate the immunostimulatory action of R-848 and CpG-B on neonatal APCs.
  
  
  
  Surface marker and cytokine secretion of APCs were evaluated after incubation of cord blood and peripheral blood mononuclear cells with the indicated adjuvants and were analyzed using flow cytometry.
  
  
  
  TLR-specific stimulation resulted in a significant induction of costimulatory molecules on neonatal APCs. Stimulation with R-848 resulted in significant higher secretion of TNFα, IL-6, IL-10, IL-12/IL-23p40, IL-12p70, and IFN-γ. Interestingly, CpG-B resulted in significant higher secretion of TNFα and IL-6.
  
  
  
  In summary, the incubation of TLR-agonists induced activation and maturation of neonatal APCs. These data show that modern TLR-specific adjuvants achieve a direct effect and potent upregulation of activation and maturation markers and cytokines in preterm neonates. We thus conclude that agents triggering TLRs might possibly overcome neonatal lack of vaccine responses.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Division of Neonatology, Paediatric Intensive Care & Neuropaediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Simone
authors.initials: S
authors.lastname: Schüller
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Division of Neonatology, Paediatric Intensive Care & Neuropaediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Wisgrill
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Division of Neonatology, Paediatric Intensive Care & Neuropaediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Kambis
authors.initials: K
authors.lastname: Sadeghi
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Division of Neonatology, Paediatric Intensive Care & Neuropaediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Erich
authors.initials: E
authors.lastname: Gindl
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.
authors.forename: Hanns
authors.initials: H
authors.lastname: Helmer
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Husslein
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Division of Neonatology, Paediatric Intensive Care & Neuropaediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Berger
authors.affiliation: Department of Surgery, Research Labs & Core Facility Flow Cytometry, Medical University of Vienna, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Spittler
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Division of Neonatology, Paediatric Intensive Care & Neuropaediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Förster-Waldl
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D064368:Healthy Volunteers; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007107:Immune System; D007231:Infant, Newborn; D007234:Infant, Premature; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D007093:Imidazoles; D009838:Oligodeoxyribonucleotides; D051193:Toll-Like Receptors; C402365:resiquimod