Lipid nanoparticles adjuvanted with poly(I:C) enhance respiratory mucosal immunity induced by a protein subunit vaccine

Subunit vaccines are typically given through injections, which limits mucosal immunity. Most adjuvants do not stimulate mucosal responses but using lipid nanoparticles (LNPs) encapsulating polyinosinic-polycytidylic acid (poly(I:C)), a toll-like receptor 3 agonist, could enhance the immune response in the lungs. We tested LNPs made from four ionizable lipids using a microfluidic mixing method to encapsulate poly(I:C) at different concentrations. The LNPs were evaluated for particle size, polydispersity index (PDI), poly(I:C) encapsulation efficiency (EE %), morphology, and NF-κB activation over a 4-week period. Mice were immunized with LNPs containing poly(I:C) and a protein antigen from Mycobacterium tuberculosis via the intrapulmonary route. Results showed that LNPs formulated with low molecular weight poly(I:C) exhibited the most favorable physicochemical properties and higher NF-κB induction compared to those made with high molecular weight poly(I:C), although a statistically significant difference was only observed for PDI. LNPs made with the ionizable lipid SM-102 were the most stable. Immunized mice had enhanced levels of serum and mucosal antibodies. Notably, the most prominent effect of the poly(I:C)-LNPs was the generation of significant cytokine-producing cells in the lungs and spleen, alongside memory cells in the lungs, spleen, and lymph nodes. In conclusion, pulmonary immunization with poly(I:C)-LNPs induced both systemic and mucosal immunity, though further investigation into antigen-specific protection is necessary. Overall, this work demonstrates new possibilities for vaccine development against respiratory infections.

Abstract from PubMed (PMID 43003275). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.