Positively charged nanocomplex modulates dendritic cell differentiation to enhance Th1 immune response.

Abstract

Most existing vaccines use activators that polarize the immune response to T-helper (Th) 2 response for antibody production. Our positively charged chitosan (Cs)-based nanocomplex (CNC) drives the Th1 response through unknown mechanisms. As receptors for the positively charged CNC are not determined, the physico-chemical properties are hypothesized to correlate with its immunomodulatory effects. To clarify the effects of surface charge and size on the immune response, smaller CNC and negatively charged CNC encapsulating ovalbumin are tested on dendritic cell (DC) 2.4​cells. The negatively charged CNC loses activity, but the smaller CNC does not. To further evaluate the material effects, we replace Cs by poly-amino acids. Compared with the negatively charged nanocomplex, the positively charged one preserves its activity. Using immature bone marrow-derived DCs (BMDC) enriched from BALB/c mice as a model to analyze DC differentiation, treatments with positively charged nanocomplexes evidently increase the proportions of Langerin+ dermal DC, CD11blo interstitial DC, and CD8a+ conventional DC. Additionally, vaccination with two doses containing positively charged nanocomplexes are safe and increase ovalbumin-specific IgG and recall T-cell responses in mice. Overall, a positive charge seems to contribute to the immunological effect of nanocomplexes on elevating the Th1 response by modulating DC differentiation.