Cationic Nanogel Coated Norovirus VLP Nasal Vaccine Induces Neutralizing Mucosal IgA and Serum IgG Antibodies

Although norovirus can affect people of any age, the majority of deaths and illnesses occur in children under one year old and people over the age of 55. Currently, there is no vaccine or medication available. Previously, we developed a nasal vaccine drug delivery system (DDS) for a small protein antigen by using cationic cholesteryl pullulan (cCHP) nanogels, in which the vaccine antigen was embedded in the nanogel structure through hydrophobic interactions. Here, we developed and tested a virus-like particle (VLP)-based nasal vaccine system that is coated in nanogel. We used VLPs (diameter, approximately 40 nm) of the GII.4 (Sydney_2012) genotype of norovirus, a globally prevalent strain. By using a molar ratio of 1:10 or 1:100 VLPs to nanogel, we successfully covered the VLPs with cationic nanogel by electrostatic force. Following nasal immunization in mice, the nanogel-covered VLPs bound continuously to the nasal epithelium, effectively enabling mucosal dendritic cells to take them up and initiate systemic antigen-specific IgG and IgA antibody responses as well as antigen-specific IgA antibodies in mucosal compartments such as the airways and intestinal tract. The antibodies induced by nasal immunization with the nanogel-covered VLP vaccine neutralized the GII.4 (Sydney_2012) genotype of norovirus. These results provide proof of concept for advancing the development of adjuvant-free cCHP-nanogel-based VLP nasal vaccines.