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

Abstract

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.

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