Nanoparticle orientationally displayed antigen epitopes improve neutralizing antibody level in a model of porcine circovirus type 2

Ding, Peiyang; Zhang, Teng; Li, Yafei; Teng, Man; Sun, Yaning; Liu, Xiao; Chai, Shujun; Zhou, Enmin; Jin, Qianyue; Zhang, Gaiping

Nanoparticles offer new horizons for subunit vaccine design. 44 The most important mechanisms of nanoparticles in improving subunit vaccine effectiveness are by increasing the amount of antigen taken by APCs and multiplying the displayed subunit antigens in well-ordered arrays. 18, 19 Nanoparticles provide a customizable method for ligation of antigens by linking specific sites such as thiol groups to the gold particle. Furthermore, phosphorylation sites on proteins have a high affinity for aluminum hydroxide nanoparticles and tag polypeptides on antigens or domains on fusion-expressing antigens can be linked to nanoparticles, for example, poly-histidine tags can bind to various divalent High-resolution structures provide an opportunity to understand the structural basis for immunogenicity and immunodominance, improve vaccine efficacy, and broaden the range of vaccine-preventable diseases. 45 According to the structural information of antigens, complete exposure of conserved or hidden neutralizing epitopes is the basic principle of structural vaccinology. 46 Self-assembling protein nanoparticles have been used to achieve targeted display of antigens. 18 Kanekiyo et al used a structure-based design strategy to generate a genetic fusion encoding hemagglutinin (HA) of influenza virus linked to ferritin. Interestingly, ferritin forms a nearly spherical particle composed of 24 subunits. HA was exposed on the outer surface of ferritin, mimicked its spatial position on the influenza H1N1 virus, and elicited broad NA against influenza virus. 47 The fusion of the aminoterminus and carboxyl-terminus of the target antigen with the protein nanoparticles confines the spatial conformation of the antigen and thus it may be unfavorable to randomly select a connection point and the orientationally display of the antigen. 48, 49 Furthermore, a protein carrier is immunogenic, which is disadvantageous for the development of similar vaccines. These are limited to widely used structure-based nanoparticles in directional display strategy.