The use of layered double hydroxides as DNA vaccine delivery vector for enhancement of anti-melanoma immune response

Abstract

Our previous studies have shown that Mg:Al 1:1 layered double hydroxides (LDH(R1)) nanoparticles could be taken up by the MDDCs effectively and had an adjuvant activity for DC maturation. Furthermore, these LDH(R1) nanoparticles could up-regulate the expression of CCR7 and augment the migration of DCs in response to CCL21. In current study, we have evaluated whether LDH(R1) as DNA vaccine delivery carrier can augment the efficacy of DNA vaccine immunization in vivo. Firstly, we found that LDH(R1) was efficient in combining DNA and formed LDH(R1)/DNA complex with an average diameter of about 80-120 nm. Its high transfection efficiency in vivo delivered with a GFP expression plasmid was also observed. After delivery of pcDNA(3)-OVA/LDH(R1) complex by intradermal immunization in C57BL/6 mice, the LDH(R1) induced an enhanced serum antibody response much greater than naked DNA vaccine. Using B16-OVA melanoma as tumor model, we demonstrated that pcDNA(3)-OVA/LDH(R1) complex enhanced immune priming and protection from tumor challenge in vivo. Furthermore, we showed that LDH(R1) induced dramatically more effective CTL activation and skewed T helper polarization to Th1. Collectively, these findings demonstrate that this LDH(R1)/DNA plasmid complex should be a new and promising way in vaccination against tumor.