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

TY - JOUR

T1 - A stable nanoparticulate DDA/MMG formulation acts synergistically with CpG ODN 1826 to enhance the CD4(+) T-cell response

AU - Karlsen, Kasper

AU - Korsholm, Karen Smith

AU - Mortensen, Rasmus

AU - Ghiasi, Seyed Mojtaba

AU - Andersen, Peter

AU - Foged, Camilla

AU - Christensen, Dennis

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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.

AB - 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.

U2 - 10.2217/nnm.14.197

DO - 10.2217/nnm.14.197

M3 - Journal article

C2 - 25529567

SN - 1743-5889

VL - 9

SP - 2625

EP - 2638

JO - Nanomedicine

JF - Nanomedicine

IS - 17

ER -