Recent Advances in Drug Delivery and Formulation · 6 authors, 2 centres
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This review examines patented nanoadjuvant-based nasal vaccines, highlighting how lipid and polymer nanocarriers enhance antigen delivery and immune response. Nanoadjuvants improve antigen stability, mucosal adhesion, and controlled release, enabling both systemic and mucosal immunity. The findings underscore the potential of nanoadjuvants as core intellectual property for developing effective intranasal vaccines against infectious diseases.
**Background:** The nasal mucosa is an attractive route for vaccination due to its ease of administration, high vascularization, and presence of immunocompetent cells. However, purified antigens often lack immunogenicity, necessitating adjuvants. Nanoadjuvants—nanomaterials that enhance antigen delivery and modulate immune responses—are central to innovative nasal vaccine formulations. This review analyzes patented compositions and manufacturing methods for nanoadjuvant-based nasal vaccines, focusing on how these systems influence immune responses.
**Methods:** The authors conducted a review of peer-reviewed literature and patents related to nasal vaccines containing nanoadjuvants. They categorized nanocarriers into lipid-based (liposomes, ISCOMs, virosomes, proteosomes, nanoemulsions) and polymer-based (polyester nanoparticles, lectin-targeted carriers, polysaccharide-based carriers, especially chitosan). Patents were selected to illustrate diverse formulations—liquid, gel/semi-solid, and solid (powder) compositions—and their claimed advantages.
**Key Results:** The review describes multiple patented nanoadjuvant systems: - **Lipid-based nanocarriers:** Liposomes enhance mucosal immunity when administered intranasally but often require co-stimulants. ISCOMs (40 nm) induce Th1 and CTL responses but are limited to animal vaccines due to Quil A toxicity; nasal administration reduces this toxicity. Nanoemulsions (50–1000 nm) improve mucoadhesion and antigen permeation; patents describe oil-in-water nanoemulsions for MRSA (CN105251002), anthrax (US2017007689), and RSV (US2017360919). - **Polymer-based nanocarriers:** Chitosan-based systems (e.g., US6391318) enhance nasal residence time and induce both serum IgG and secretory IgA. Patents describe chitosan nanospheres for RSV (US2007009951) and cationic nanogels (JP2010105968) that act as artificial chaperones. - **Solid formulations:** Dry powder vaccines (e.g., CN104208029, AU2012244077) use freeze-drying with stabilizers like trehalose to preserve antigen structure and induce mucosal and systemic immunity. One patent (116) describes a powder containing a nanoemulsion adjuvant and calcium carbonate carrier for Mycoplasma hyopneumoniae, showing equivalent IFN-γ responses to intramuscular immunization. - **Other innovations:** Patents include ionic nanoparticles (KR20050017770), micellar nanoparticles targeting CETP for atherosclerosis (US2015328296), and mucosal adjuvants combining oligo-chitosan with lymphotactin plasmids (CN102688488).
**Clinical Implications:** Nanoadjuvants enable nasal vaccines that induce both mucosal (sIgA) and systemic (IgG) immunity, potentially improving compliance and enabling mass immunization without needles. However, many systems remain preclinical; challenges include toxicity (e.g., Quil A), stability, and need for further clinical validation. The review emphasizes that nanoadjuvants are often the core intellectual property of innovative nasal vaccines, suggesting a strong commercial and research focus. Future developments should address safety, scalability, and regulatory approval to translate these technologies into clinical use.