A stable nanoparticulate DDA/MMG formulation acts synergistically with CpG ODN 1826 to enhance the CD4+ T-cell response. (December 2014)

• Record Type: Journal Article
• Authors: Karlsen, Kasper; Korsholm, Karen Smith; Mortensen, Rasmus; Ghiasi, Seyed Mojtaba; Andersen, Peter; Foged, Camilla; Christensen, Dennis
• Is Part Of: Nanomedicine. Volume 9:Number 17(2014)
• Page Start: 2625
• Page End: 2638
• Publication Date: 2014-12
• Subjects: adjuvant -- cationic liposome -- CD4+ T cells -- CpG -- pattern-recognition receptors; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm.14.197
• Languages: English
• ISSNs: 1743-5889

Abstract

Aim: 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.Materials & 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.Conclusion: The nanoparticulate DDA/MMG/CpG adjuvant can be stabilized and synergistically enhances CD4 + T-cell responses compared with DDA/MMG liposomes.