Encapsulating K- and D-type CpG ODNs within liposomes enhances and broadens their as vaccine adjuvants

Authors

• BH Horuluoglu
• I Gursel
• DM Klinman

Abstract

Liposomes are promising candidates for encapsulating bioactive agents due to their high entrapment efficiency and protective capacity. Although both D and K type CpG ODN are strictly dependent on TLR9, K ODN trigger pDCs to mature and secrete TNFa while D ODN stimulate pDC to produce IFNa. When cells are incubated with a mixture of K and D ODN, K masks the activity of D. As the use of both K and D ODN would be of benefit when preparing vaccine adjuvants and for immunotherapy, we reasoned that their co-encapsulation in liposomes might enable both types of immune activation. Our data indicate that simultaneous delivery of D ODN loaded into neutral liposomes plus K ODN loaded into cationic liposomes improved rather than masked IFNa production while continuing to support TNFa by PBMCs. Confocal microscopy studies showed that liposomal encapsulation does not change the subcellular localization of either class of ODN. However uptake and binding experiments showed that encapsulation in cationic liposomes slows and reduces the uptake of K ODN whereas neutral encapsulation of D increases their uptake by pDCs. This change in uptake may explain the observed benefit of liposomal encapsulation when compared to their free form. The efficiency of K plus D liposome combinations was examined in a murine tumor vaccine model. The liposome combinations induced pronounced Th1-biased anti-OVA immunity and led to a significant reduction of B16-OVA tumors following inoculation. This study demonstrates that the beneficial features of D and K ODN could be obtained simultaneously by appropriate liposomal formulation, further extending the breadth of CpG ODN-dependent immunotherapy

Scientific Focus Area: Immunology

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