This example highlights the importance of driving higher-order molecular structure in modern vaccines. The major vault protein (MVP) is another kind of self-assembling protein. Ninety-six units of MVP can self-assemble into a barrel-shaped vault nanoparticle, with a size of approximately 40 nm wide and 70 nm long [127]. Antigens that are genetically fused with a minimal interaction domain can be packaged inside vault nanoparticles by self-assembling process when mixed with MVPs [127]. Vault nanoparticles

have been used to encapsulate the major outer membrane protein of Chlamydia muridarum for studies of mucosal immunity [127]. Another type of nanoparticles used as adjuvants in vaccines delivery is nano-sized emulsions [100], [128] and [129]. These nanoparticles can exist as oil-in-water or water-in-oil forms, where the droplet size can vary from 50 nm to 600 nm [128]. Selleck MS275 Emulsions can carry antigens inside their core for efficient vaccine delivery [128] or can also be simply mixed with the antigen. One

commonly-used emulsion is MF59™, an oil-in-water emulsion which has been licensed as a safe and potent vaccine adjuvant in over 20 countries [35] and [130]. It has been widely studied for use in influenza vaccines [130], [131] and [132]. Another is Montanide™, a large family of both oil-in-water and water-in-oil emulsions, including ISA 50 V, 51, 201, 206 and 720 [35] and [133]. Montanide ISA 51 and 720 have been used in Malaria vaccines [134] and [135], Montanide ISA 201 PFI-2 nmr and 206 have been used in foot-and-mouth disease vaccines [136]. Recently, a tailorable nano-sized emulsion (TNE) platform technology has been developed using non-covalent

click self-assembly for antigen and drug delivery [137] and [138]. An oil-in-water nanoemulsion is formed using designed biosurfactant peptides and proteins. Using a self-assembling peptide-protein system, immune-evading PEG and a receptor-specific antibody can be arrayed in a selectively proportioned fashion on the aqueous interface of a nano-sized oil-in-water emulsion (Fig. 4). Targeted delivery of protein antigen to dendritic cells was achieved [138]. This work demonstrates from a new and simple way to make biocompatible designer nanoemulsions using non-covalent click self-assembly by sequential top-down reagent addition. Vaccine formulations comprising nanoparticles and antigens can be classified by nanoparticle action into those based on delivery system or immune potentiator approaches. As a delivery system, nanoparticles can deliver antigen to the cells of the immune system, i.e. the antigen and nanoparticle are co-ingested by the immune cell, or act as a transient delivery system, i.e. protect the antigen and then release it at the target location [79]. For nanoparticles to function as a delivery system, association of antigen and nanoparticle is typically necessary.