title: Adjuvant effect of microencapsulated NOD ligands studied in a human phagocytic cell line.
abstract: BACKGROUND
  Modern subunit vaccines, which are of high purity compared with traditional vaccines, are often incapable of inducing strong immune responses as necessary to build an immunological memory. The desired level of immune response can be achieved only by codelivering immune-modulating agents along with the antigenic epitopes present in these high-purity formulations. This study aimed to explore the adjuvant effect of nucleotide oligomerization domain (NOD) receptor agonists as immunomodulators encapsulated in polymeric microparticles as carriers.
  
  
  METHODS
  Microparticles (MP) prepared from poly[(rac-lactide)-co-glycolide] (PLGA) (Mn = 5 kDa, PD = 3.2) by the water-in-oil-in-water (w/o/w) emulsion/solvent evaporation technique were characterized in terms of size, surface morphology, payload and endotoxin content. As NOD agonists, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP; NOD 2) and γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP; NOD 1) were encapsulated. The immunomodulatory potential of these ligand-loaded MP was evaluated with a human acute monocytic leukemia cell line (THP-1X Blue-CD14 cells).
  
  
  RESULTS
  The MP prepared had a phagocytosable size (<10 µm) with a unimodal size distribution and low endotoxin content (<0.5 EU/mL). A dose-dependent cell activation could be established for MDP-loaded microparticles.
  
  
  CONCLUSIONS
  MP with suitable characteristics for phagocytosis can be prepared and loaded with NOD agonists. The capability of these ligand-loaded microparticles to activate monocytes suggests their broader exploration as vaccine carriers.
authors.affiliation: Center for Biomaterial Development, Institute of Polymer Research, Helmholtz-Zentrum Geesthacht, Teltow, Germany.
authors.forename: Simi
authors.initials: S
authors.lastname: Mathew
authors.forename: Toralf
authors.initials: T
authors.lastname: Roch
authors.forename: Marco
authors.initials: M
authors.lastname: Frentsch
authors.forename: Andreas
authors.initials: A
authors.lastname: Lendlein
authors.forename: Christian
authors.initials: C
authors.lastname: Wischke
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000737:chemistry / Q000378:metabolism; D000276:Adjuvants, Immunologic; D002460:Cell Line; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D004339:Drug Compounding; D004655:Emulsions / Q000737:chemistry; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008024:Ligands; D008863:Microspheres; D053472:Nod Signaling Adaptor Proteins / Q000819:agonists* / Q000378:metabolism; D009821:Oils / Q000737:chemistry; D010586:Phagocytes / Q000166:cytology / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D022223:Vaccines, Subunit / Q000276:immunology; D014867:Water / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D004655:Emulsions; D008024:Ligands; D053472:Nod Signaling Adaptor Proteins; D009821:Oils; D022223:Vaccines, Subunit; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D003960:Diaminopimelic Acid; C034331:N(2)-(gamma-D-glutamyl)-meso-2,2'-diaminopimelic acid