Adjuvant-free nanogel-based PspA nasal vaccine for the induction of protective immunity against Pneumococcus

Abstract To establish strategically effective and attractive vaccine against pneumococcal respiratory infections, combining the current knowledge and technology for common antigen throughout pneumococcal strains and the new delivery system is essential. Here, we introduce a new pneumococcal nasal vaccine using the advantages of Pneumococcal surface protein A (PspA) antigen and a new adjuvant-free intranasal vaccine-delivery system with a nanometer-sized hydrogel (nanogel) consisting of a cationic type of cholesteryl group-bearing pullulan (cCHP). Nanogel-based PspA nasal vaccination induced high levels of antigen-specific serum IgG, and nasal and bronchial secretory IgA (SIgA) antibodies. The levels of PspA-specific antibodies were as high as those in mice nasally immunized with PspA and mucosal adjuvant, cholera toxin. The nanogel induced PspA-specific immune responses provided protective immunity against the lethal challenge with Streptococcus pneumoniae Xen10. Nanogel-PspA vaccinated group thus had less numbers of pneumococcus on the surface of the bronchial mucosa, and perfectly protected from the pneumococcal invasion of the lung parenchyma. These results demonstrate the effectiveness of the nanogel-based PspA nasal vaccine system as an adjuvant free mucosal vaccine against the respiratory infection of pneumococcus.