Hyaluronic acid (HA)-coated biodegradable polymeric micelles were developed as nanoparticulate vaccine delivery systems to establish an effective nasal vaccine. We previously reported HA-coated micelles prepared by forming a polyion complex (PIC) of poly(L-lysine)-b-polylactide (PLys⁺-b-PLA) micelles and HA. The HA-coated micelles exhibited specific accumulation in HA receptor-expressing cells and extremely high colloidal stability under diluted blood conditions. In this study, a model antigen, ovalbumin (OVA), and an adjuvant oligonucleotide containing the CG motif (CpG-DNA) were efficiently loaded in HA-coated micelles via electrostatic interactions. HA-coated micelles delivered OVA and CpG-DNA in mouse bone marrow-derived dendritic cells (BMDCs) and resulted in upregulation of mRNA encoding IFN-γ and IL-4 in BMDCs. In addition, HA-coated micelles enhanced the expression of the major histocompatibility complex (MHC) class II on BMDCs. We investigated the immune response of HA-coated micelles following intranasal administration. HA-coated micelles induced higher OVA-specific IgG in the blood and OVA-specific IgA in the nasal wash than control (carboxymethyl dextran-coated) micelles. These results suggest that HA-coated micelles efficiently deliver antigens and adjuvants to mucosal-resident immune cells. Therefore, HA-coated micelles are promising platforms for developing nasal vaccines against infectious diseases.

This work was financially supported in part by the Private University Research Branding Project: Matching Fund Subsidy from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) Japan (2016–2020), Grants-in-Aid for Scientific Research (20H00670) from the Japan Society for the Promotion of Science (JSPS), and Kansai University Contingency Fund for Education and Research Outlay (2020).

2020年度関西大学教育研究緊急支援経費 研究課題「高分子ミセルを用いた対コロナウイルス経鼻型ワクチンの開発」