As ordered nanoscale architectures, viruses and virus-like particles (VLPs) remain unsurpassed by synthetic strategies to produce uniform and symmetric nanoparticles. Maintaining or mimicking the symmetry of pathogenic viruses, VLPs offer a ready platform for facilitating recognition, uptake, and processing by the immune system. An emerging understanding of how viruses interact with the immune system offers a means of precisely designing nanoparticles for biomedical use, both with respect to the structure of the particle as well as their ability to stimulate the immune system. Here we discuss recent advances by our group toward two parallel and complementary applications of VLPs, derived primarily from plants, bacteriophage, and nonviral sources, in biomedicine: diagnostic imaging and rational vaccine design. First we discuss advances in increasing VLP payloads of gadolinium magnetic resonance imaging (MRI) contrast agent as well as controlling the characteristics of individual gadolinium containing molecules to increase efficacy. In order to better understand the in vivo potential of VLP constructs, we then discuss the interface of protein-cages and the immune system beginning with the nonspecific innate immune system stimulation and continuing into the use of non-pathogenic VLPs as scaffolds for specific antigen presentation and control of the immune response.
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