A chitosan-based nanosystem as pneumococcal vaccine delivery platform

Chitosan-based nanosystems have been described as interesting tools for antigen delivery and for enhancing the immunogenicity of nasally administered vaccines. As a possible vaccine delivery method, the chemical conjugation of chitosan nanocapsules with the Streptococcus pneumoniae cell membrane protein PsaA (pneumococcal surface adhesin A) is suggested here. The antigen PsaA, common to all pneumococcus serotypes, is expected to improve its uptake by immune cells and to activate specific T cells, generating an adaptive immune response against pneumococcus. With this aim, chitosan nanocapsules with thiol-maleimide conjugation between the polymer (chitosan) and the antigen (PsaA) were designed to enable the surface presentation of PsaA for immune cell recognition. Spherical-shaped particles, with a size of 266 +/- 32 nm, positive charge of +30 +/- 1 mV, and good stability profiles in simulated nasal fluids (up to 24 h) were achieved. PsaA association rates were three times higher compared with nanocapsules without covalent polymer-protein conjugation. Cytotoxicity studies in cell culture media showed non-toxic effect under 150 mu g/mL concentration of nanocapsules, and subsequent studies on the maturation of immature dendritic cells in the presence of antigen-conjugated nanocapsules displayed peripheral blood mononuclear cell activation and lymphocyte differentiation after their presentation by dendritic cells. Secretion of TNF alpha following exposure to nanocapsules and the ability of nanocapsules to activate CD4 and CD8 T lymphocytes had also been studied.

Automated summary

Chitosan-based nanosystems conjugated with Streptococcus pneumoniae cell membrane protein PsaA have shown promising results in enhancing antigen uptake by immune cells and activating specific T cells, thus generating an adaptive immune response against pneumococcus. The designed nanocapsules, with good stability and positive charge, displayed increased association rates with PsaA compared to non-covalent conjugation, and exhibited no cytotoxic effects at certain concentrations in cell culture media. Furthermore, the nanocapsules were shown to activate CD4 and CD8 T lymphocytes, as well as promote the maturation of immature dendritic cells, suggesting their potential as a nasal vaccine delivery method.