Highlights from the latest articles on vaccine development using nanoparticles.

Abstract

2014 Designer aluminum salt-based nanoparticles as vaccine adjuvants Evaluation of: Sun B, Ji Z, Liao Y et al. Engineering an effective immune adjuvant by designed control of shape and crystallinity of aluminum oxyhydroxide nanoparticles. ACS Nano. 7(12), 10834–10849 (2013). Aluminum salts, such as aluminum hydroxide, are widely used in vaccines to improve antigen-specific immune responses [1]. Despite their widespread usage, the exact mechanism of their action is still not fully elucidated. Recently, NLPR3 inflammasome, also known as NALP3 or cryopyrin, has been implicated in the immunostimulatory effects observed with aluminum salts [2]. Structural studies using x-ray diffraction and infrared spectroscopy have shown that aluminum hydroxide adjuvant is actually crystalline aluminum oxyhydroxide, as opposed to aluminum hydroxide or Al(OH) 3 . The geometrical shape of the adjuvant in general has also been implicated in its uptake by antigen-presenting cells (APCs). In this study, Sun et al. designed aluminum oxyhydroxide nanoparticles with different morphologies, shapes and hydroxide concentrations and investigated their adjuvant activities [3]. They studied the effect of these parameters on aluminum oxyhydroxide’s ability to trigger the NLPR3 inflammasome and APC uptake, relative to a commercial alum preparation, using in vitro assays and in vivo studies. An aluminum oxyhydroxide library of nanorods, nanoplates and nano polyhedra was synthesized using a hydrothermal method and structures confirmed by transmission electron microscopy, x-ray diffraction, thermogravimetric analysis and Fourier transform infrared spectroscopy analyses. All the nanostructures were able to activate the NLRP3 inflammasome through generation of oxidative stress in THP-1 human monocytes and induce maturation of mouse bone marrow derived dendritic cells and IL-1β cytokine production by them, but the nanorods were more effective than the nanoplates, nanopolyhedra and the commercial alum. The nanorods were hence used in an in vivo immunization study using ovalbumin (OVA) as a model antigen. The OVA-specific immune responses induced by the OVA-adsorbed aluminum oxyhydroxide nanorods tended to be stronger than that induced by OVA-adsorbed on the commercial alum preparation. This study opens the possibility of engineering designer aluminum salt-based adjuvants with a stronger adjuvant activity.