We then conclude with remarks about the further potential and future prospects for prophylactic nanovaccinology. A great variety of synthetic polymers are used to prepare nanoparticles, such as poly(d,l-lactide-co-glycolide) (PLG) [22], [23] and [24], poly(d,l-lactic-coglycolic

acid)(PLGA) [22], [25], [26], [27], [28], [29] and [30], poly(g-glutamic acid) (g-PGA) [31] and [32], poly(ethylene glycol) (PEG) [24], and polystyrene [33] and [34]. PLG and PLGA nanoparticles have been the most extensively investigated due BYL719 clinical trial to their excellent biocompatibility and biodegradability [35] and [36]. These polymeric nanoparticles entrap antigen for delivery to certain cells or sustain antigen release by virtue of their slow biodegradation rate [27],

[28], [29], [31] and [36]. PLGA has been used to carry antigen derived from various pathogens including Plasmodium vivax with mono-phosphoryl lipid A as adjuvant [37], hepatitis B virus (HBV) [22], Bacillus anthracis [29], and model antigens such as ovalbumin and tetanus toxoid [26] and [27]. g-PGA nanoparticles are comprised of amphiphilic poly(amino acid)s, which self-assemble into nano-micelles with a hydrophilic outer shell and a hydrophobic inner core [31] and [32]. g-PGA nanoparticles are generally used to encapsulate hydrophobic antigen [31] and [32]. Polystyrene nanoparticles can conjugate to a variety of antigens as they can be surface-modified

with various functional groups [33] and [38]. Natural polymers based on polysaccharide have also been used to prepare find more nanoparticle adjuvants, such as pullulan [39] and [40], alginate [41], inulin [42] and [43], and chitosan [44], [45], [46], [47], [48] and [49]. In particular, chitosan-based nanoparticles have been widely studied due to their biocompatibility, biodegradability, nontoxic nature and their ability to be easily modified into desired shapes and sizes [31], [50] and [51]. These nanoparticles have been used in the preparation of various vaccines including HBV vaccines [49], Newcastle disease vaccines [48], and DNA vaccines [44], [46] and [47]. Inulin, a first well-known activator of complement via the alternative pathway [52], is also a potent adjuvant. Nanoparticle adjuvants derived from inulin, such as Advax™, have shown enhancement of immune response in vaccines against various viruses including influenza [42] and hepatitis B [43]. Polymers, such as Poly(L-lactic acid) (PLA), PLGA, PEG, and natural polymers such as polysaccharides [41], [53], [54] and [55], have also been used to synthesize hydrogel nanoparticles, which are a type of nano-sized hydrophilic three-dimensional polymer network. Nanogels have favorable properties including flexible mesh size, large surface area for multivalent conjugation, high water content, and high loading capacity for antigens [55] and [56].