Gemini nanoparticles as a co-delivery system for antigen – CpG oligodeoxynucleotide adjuvant combination

Abstract

Enhancement of antigen-specific immune responses could be achieved by co-delivery of antigens and adjuvants. CpG oligodeoxynucleotides (unmethylated cytosine-guanine tandems in a specific sequence; ODNs) increase innate and antigen-specific immune responses. Effective co-delivery approaches of CpG ODNs and antigens to antigen-presenting cells are needed to achieve more potent antigen-specific immune responses. We evaluated both cellular and humoural immune responses triggered by hen egg lysozyme (HEL), a model antigen, and CpG ODNs formulated in gemini surfactant and dioleoyl phosphatidylcholine-based nanoparticles as an intradermal and topical co-delivery system in a murine animal model. Overall, intradermal injection of HEL/CpG nanoparticles induced a more pronounced Th1 immune response compared with the HEL and HEL/CpG topical formulations, as evidenced by the shift in the Th2 response triggered by the antigen alone to a mixed Th1/Th2 immune response and increased the presence of interferon-gamma (IFN-γ) secreting cells in the spleen. However, in case of topical administration, the nanoparticle formulation of HEL produced enhanced immune response and immunomodulation even without the incorporation of CpG. The HEL-specific immune response and Th1 bias demonstrated the advantage of co-delivery of HEL/CpG ODNs by gemini nanoparticles intradermally, whereas, the adjuvant effect of the nanoparticle delivery system itself was more significant after topical treatment.