Spherical nucleic acids as an infectious disease vaccine platform

Despite recent efforts demonstrating that organization and presentation of vaccine components are just as important as composition in dictating vaccine efficacy, antiviral vaccines have long focused solely on the identification of the immunological target. Herein, we describe a study aimed at exploring how vaccine component presentation in the context of spherical nucleic acids (SNAs) can be used to elicit and maximize an antiviral response. Using COVID-19 as a topical example of an infectious disease with an urgent need for rapid vaccine development, we designed an antiviral SNA vaccine, encapsulating the receptor-binding domain (RBD) subunit into a liposome and decorating the core with a dense shell of CpG motif toll-like receptor 9 agonist oligonucleotides. This vaccine induces memory B cell formation in human cells, and in vivo administration into mice generates robust binding and neutralizing antibody titers. Moreover, the SNA vaccine outperforms multiple simple mixtures incorporating clinically employed adjuvants. Through modular changes to SNA structure, we uncover key relationships and proteomic insights between adjuvant and antigen ratios, concepts potentially translatable across vaccine platforms and disease models. Importantly, when humanized ACE2 transgenic mice were challenged in vivo against a lethal live virus, only mice that received the SNA vaccine had a 100% survival rate and lungs that were clear of virus by plaque analysis. This work underscores the potential for SNAs to be implemented as an easily adaptable and generalizable platform to fight infectious disease and demonstrates the importance of structure and presentation in the design of next-generation antiviral vaccines

Pilot study of the multicentre DISCHARGE trial: image quality and protocol adherence results of computed tomography and invasive coronary angiography (vol 30, pg 1997, 2020)

The original version of this article, published on 16 December 2019, unfortunately contained two mistakes.Cardiovascular Aspects of Radiolog

CO2 reduction on supported Ru/Al2O3 catalysts: Cluster size dependence of product selectivity

The catalytic performance of a series of Ru/Al2O3 catalysts with Ru content in the 0.1-5% range was examined in the reduction of CO2 with H2. At low Ru loadings (???0.5%) where the active metal phase is highly dispersed (mostly atomically) on the alumina support, CO is formed with high selectivity. With increasing metal loading, the selectivity toward CH4 formation increases, while that for CO production decreases. In the 0.1% Ru/Al2O3 catalyst, Ru is mostly present in atomic dispersion, as scanning transmission electron microscopy (STEM) images obtained from the fresh sample prior to catalytic testing reveal. STEM images recorded from this same sample, following the temperature programmed reaction test, clearly show the agglomeration of small metal particles (and atoms) into 3D clusters. The clustering of the highly dispersed metal phase is responsible for the observed dramatic selectivity change during elevated temperature tests: dramatic decrease in CO and large increase in CH4 selectivity. Apparent activation energies, estimated from the slopes of Arrhenius plots, of 82 and 62 kJ/mol for CO and CH 4 formation were determined, respectively, regardless of Ru loading. These results suggest that the formation of CO and CH4 follow different reaction pathways or proceed on active centers of a different nature. Reactions with CO2/H2 and CO/H2 mixtures (under otherwise identical reaction conditions) reveal that the onset temperature of CO2 reduction is about 150 C lower than of CO reduction.close3