Immunostimulatory Pickering emulsion for oral vaccine delivery

To overcome gastric acid degradation and ensure robust immune activation, a novel Pickering emulsion stabilized by poly(lactic-co-glycolic acid) (PLGA) nanoparticles was developed for the co-delivery of vaccine antigens and adjuvants via the oral route. Pickering emulsions, stabilized by solid particles, can enhance stability and protect antigens from gastric degradation. We encapsulated a TLR7/8 agonist R848 in PLGA nanoparticles and fabricated Pickering emulsions (R848-PLGA-NP@PE) to boost immune activation, and further prepared model antigen Ovalbumin (OVA) loaded Pickering emulsion formulation (R848-PLGA-NP@PE-OVA) to induce antigen-specific immune responses. R848-PLGA-NPs can improve vaccine efficacy by serving both as a stabilizer and an adjuvant, activating antigen-presenting cells (APCs). R848-PLGA-NP@PE-OVA exhibited a uniform particle size (245 nm), stable zeta potential (-40 mV), and high antigen encapsulation efficiency (>80 %), that were tested in Simulated Intestinal Fluid (SIF) and Simulated Gastric Fluid (SGF). R848-PLGA-NP@PE exhibited enhanced uptake by and activation of dendritic cells compared to control groups. In vivo, R848-PLGA-NP@PE significantly improved CD4 + T cell, CD8 + T cell, and NK cell activation. Notably, granzyme B expression in NK cells reached 2.1 times the level of the PBS group and 1.45 times that of the Free OVA + R848 group. The OVA-specific IgG level in the R848-PLGA-NP@PE-OVA group was approximately 3.9 times that of the PBS group and 2.5 times that of the free R848 + OVA group. Fecal OVA-specific IgA levels were significantly higher than control group. The combined data suggests that Pickering emulsions fabricated with PLGA-NPs are versatile oral vaccine delivery platforms to induce cellular and humoral immune responses.