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Research Progress

New Strategy for Particulate Adjuvant Development: Dynamic Remodeling

Jan 11, 2018

To combat infectious and chronic diseases, safe and effective adjuvant platforms for prophylactic and therapeutic vaccinations are demanded. Bionic design is regarded as the golden rule in adjuvant design.

Previous attempts have focused on the size, shape, charge or compositions of the microbes or diseased cells. However, the fluidity has not been modelled.

In fact, antigens on apoptotic and cancerous cells also experience the membrane dynamic curvature and lateral diffusion to increase the contact area and multivalent interactions with antigen-presenting cells (APCs), triggering internalization and subsequent cross-presentation of antigens for robust immune responses.

Inspired by this mechanism, a research team led by Prof. MA Guanghui from State Key Laboratory of Biochemical Engineering of the Institute of Process Engineering of the Chinese Academy of Sciences re-tailored Pickering emulsion (nanoparticle stabilized emulsion), enabling it act as an elastic and biodegradable adjuvant.

By creatively combining quartz crystal microbalance with dissipation (QCM-D) and fluorescence recovery after photobleaching (FRAP), Pickering emulsion was unraveled to model after the force-dependent deformation and dynamic fluidity of the natural endocytosis targets during the cellular contact zone (Figure 1).   

 

Figure 1. PPAS is tailored for adjuvant application. (Image by IPE) 
In the absence of surfactants, the raspberry-like morphology of Pickering emulsions offers substantial specific surface area for antigen adsorption and cellular interactions. Thereafter, these special features triggered three-dimensional multivalent interactions with APCs, and subsequently stimulated potent innate and adaptive immune responses (Figure 2a-c).

Compared with the clinical relevant adjuvants (Alum, MF59, and AS04), Pickering emulsion droplets were demonstrated with the enhanced immune protections against influenza virus challenge and higher efficiency in both E.G7/OVA and B16/MUC1 anti-tumor immune therapies (Figure 2d-f).

 

Figure 2. PPAS cultivates APCs to exert systemic immune responses. (Image by IPE)

The developed Pickering emulsion was validated with high biosafety, stability and bright prospects in clinic applications, which offered an alternative strategy to exploit the force-dependent deformation and lateral mobility of particulate adjuvants for potent vaccinations (Figure 3).

Furthermore, preparation technique of uniform biodegradable particle enables the successful construction of this bionic adjuvant with high safety, providing bright application potential.

Their work entitled “Exploiting the pliability and lateral mobility of Pickering emulsion for enhanced vaccination” was published in Nature Materials.

 

Figure 3. Schematic illustration of the pliability and lateral mobility of Pickering emulsion for enhanced vaccination strategies. (Image by IPE)

 

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