More recently, other particulate adjuvants have been licensed

for human use. Emulsions like MF59 or AS03 are components of Fluad and Pandemrix, respectively [24, 25]. Other vaccines such as Epaxal [26] or Inflexal [27] include virosomes. Latest approved systems are composed of combination of adjuvants, such as AS04 (approved for human use in both Europe and USA), which comprises MPL (monophosphoril lipid A) and alum Inhibitors,research,lifescience,medical and is used into Fendrix [28] or AS04 combined with virus like particles (VLPs) used into Cervarix [29, 30] and Gardasil [31]. Table 1 Examples of EMA- and/or FDA-approved vaccines based on micro- and nanoparticulated delivery systems. MF59 and AS03 are squalene- and tocopherol-based o/w emulsions, respectively. AS04 is composed of monophosphoril lipid A and alum. Virosomes are composed … This paper summarizes micro- and nanoparticulated delivery systems used in the development of synthetic peptide-based

vaccines. We also discuss various strategies for improving their efficacy in developing an appropriate Inhibitors,research,lifescience,medical immune response (Table 2). Table 2 Schematic view of the mechanism of action and advantages of the different micro- and nanotechnologies for peptide-based vaccine delivery. 2. Inhibitors,research,lifescience,medical Micro- and Nanoparticulated Systems for Synthetic Peptide Vaccine Development 2.1. Alum Aluminium salts (generally, Al(OH)3 and AlPO4), often called alum, have been widely used in humans for more than 80 years, and, until recently, it has been the only adjuvant approved for human use in the USA [32]. Currently, there are many vaccines containing alum, such as Recombivax Inhibitors,research,lifescience,medical HB or Engerix B. Alum adjuvancity is associated with enhanced antibody responses [19]. It has been shown that after OVA-alum administration Th2 effector response is generated, as T helper cells produced IL-4, IL-5, and IL-10 but little IFN-γ [33]. In addition, Li et al. demonstrated that alum enhances the production of IL-10, a Th2 cytokine, and inhibits Inhibitors,research,lifescience,medical that of IP-10 (IFN-γ-inducible protein), a chemokine specific for Th1 cells [34].

It has been shown that alum induces rapid cell selleck compound recruitment at the injection heptaminol site. Kool et al. demonstrated that after an intraperitoneal injection of alum, a local production of chemoatractants like CCL2 and CXCL1 was triggered, as well as a recruitment of neutrophils, eosinophils, monocytes, and subsequently DCs. This study also revealed that following intraperitoneal or intramuscular administration of alum, recruited monocytes migrate to the draining lymph nodes and differenciate into inflammatory DCs capable of priming T cells [33]. Several action mechanisms have been proposed in order to explain alum adjuvancity. Previously, it was thought that alum formed a depot by which the antigen was slowly released and which converted the antigen into a particulate form, facilitating phagocytosis by APCs [35].