title: A stable nanoparticulate DDA/MMG formulation acts synergistically with CpG ODN 1826 to enhance the CD4⁺ T-cell response.
abstract: OBJECTIVE
  To combine the dimethyldioctadecyl ammonium/monomycoloyl glycerol (DDA/MMG) liposomal vaccine adjuvant with the Toll-like receptor (TLR) ligands poly(I:C) (TLR3), flagellin (TLR5) or CpG oligodeoxynucleotide 1826 (TLR9) and investigate their physicochemical properties as well as their CD4(+) T-cell-inducing capacity.
  
  
  METHODS
  Formulations were investigated by dynamic light scattering and differential scanning calorimetry. Their CD4(+) T-cell induction with a tuberculosis antigen was analyzed by multiplex cytokine analysis, ELISA and intracellular cytokine staining.
  
  
  RESULTS
  DDA/MMG/CpG was the best combination for obtaining increased CD4(+) T-cell responses. However, coformulating CpG and DDA/MMG liposomes led to instability and the formulation was therefore optimized systematically using a design of experiment.
  
  
  CONCLUSIONS
  The nanoparticulate DDA/MMG/CpG adjuvant can be stabilized and synergistically enhances CD4(+) T-cell responses compared with DDA/MMG liposomes.
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, Copenhagen S, Denmark.
authors.forename: Kasper
authors.initials: K
authors.lastname: Karlsen
authors.forename: Karen Smith
authors.initials: KS
authors.lastname: Korsholm
authors.forename: Rasmus
authors.initials: R
authors.lastname: Mortensen
authors.forename: Seyed Mojtaba
authors.initials: SM
authors.lastname: Ghiasi
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Camilla
authors.initials: C
authors.lastname: Foged
authors.forename: Dennis
authors.initials: D
authors.lastname: Christensen
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002626:Chemistry, Pharmaceutical; D004357:Drug Synergism; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D051379:Mice; D050178:Monoglycerides / Q000008:administration & dosage* / Q000737:chemistry; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage* / Q000737:chemistry; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D014612:Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology
chemical_list: C423449:CpG ODN 1826; D008081:Liposomes; D050178:Monoglycerides; D009838:Oligodeoxyribonucleotides; D000644:Quaternary Ammonium Compounds; D014612:Vaccines; C543328:monomycoloyl glycerol; C015831:dimethyldioctadecylammonium
keywords: CD4+ T cells; CpG; adjuvant; cationic liposome; pattern-recognition receptors