The naturally-optimized nanoparticle size and repetitive structural order means that VLPs induce potent immune responses, even in the absence of adjuvant [109]. VLP based vaccines are the first nanoparticle class to reach market – the first VLP vaccine for hepatitis B virus was commercialized

in 1986 [110] – and have become widely administered in healthy populations. In nanovaccinology, VLP nanoparticles have the strongest evidence base for safe use in healthy humans. Newer VLP vaccines for human papillomavirus [111] and hepatitis E [112] have been approved for use in humans in 2006 and 2011, respectively. VLPs can be derived from a variety of viruses (Fig. 3) [107], with sizes ranging from 20 nm to 800 nm [13] and [113], and can be manufactured with a variety of process technologies [114]. The historical this website approach to VLP manufacture involves an in vivo route, where the assembly of capsid proteins into VLPs occurs inside the expression host. The assembled particle is then purified away from adherent and encapsulated contaminants. In some cases it becomes necessary to disassemble and then re-assemble the VLP to improve quality [114]; recently-approved VLP vaccines typically include some aspect

of extracellular assembly within the processing regime. An emerging approach for VLP assembly is GBA3 through cell-free in vitro processing [115], [116], [117], [118] and [119]. This approach

inverts the traditional assemble-then-purify paradigm; Vemurafenib chemical structure large-scale purification of the VLP building blocks from contaminants occurs first, then these are assembled in vitro, avoiding the need to disassemble VLP structures after assembly in a cell. Further review of VLP manufacturing approaches is available elsewhere [13], [19], [120] and [121]. VLPs commercialized to date are based on self-assembly of proteins derived from the target virus. However, VLPs can also act as a delivery platform where a target antigen from a virus unrelated to the VLP used is modularized on the surface of a VLP [20], [122], [123], [124] and [125]. These modular VLPs exploit known benefits of VLPs (optimized particle size and molecular structure) to target disease in an engineered fashion. With many VLP vaccines currently in clinical or pre-clinical trials [13] and [19], an increase in the number of approved VLP-based vaccines can be expected. Recognizing the power of the VLP approach, self-assembling systems that attempt to drive higher levels of protein quaternary structuring have emerged for the preparation of nanoparticle-based vaccines. Ferritin is a protein that can self-assemble into nearly-spherical 10 nm structure [126].