Moreover, a recent clinical trial suggests that Pandemrix used in children 6–35 months old is highly immunogenic and that overall reactogenicity profile is acceptable although reactions including fever tend to increase after a second dose [54]. However, to our knowledge, no study has been published that combines the use of synthetic peptides and MF59 or AS03. Inhibitors,research,lifescience,medical Belnacasan mouse Montanide is a w/o emulsion-based adjuvant. Although it is not yet approved for human use, lot of clinical trials are undergoing against several diseases such as malaria, melanoma, or nonsmall

cell lung cancer [55]. A study carried out in our laboratory, compared the immune response against the S3 malarial synthetic peptide using Montanide, poly-lactide-co-glicolide (PLGA) microparticles and aluminium hydroxide. Subcutaneously administered Montanide and microspheres resulted in effective adjuvants and revealed mixed Th1/Th2 immune responses [56]. However, in a previous study Inhibitors,research,lifescience,medical it was shown that Montanide was effective in eliciting antibodies against the 3D7 peptide but not against the FC27 peptide [57]. In addition, a recent clinical trial

has been carried out to evaluate the safety, tolerability, and immunogenicity of mixtures of N, R, and C long synthetic peptides derived from the P. vivax circumsporozoite protein formulated in two types of Montanide (ISA 720 and ISA 51) [58]. However, the results of Inhibitors,research,lifescience,medical this study are not yet published. 2.3. Polymeric Micro- and Nanoparticles Polymeric micro- and nanoparticle-based vaccine delivery systems have been widely studied. The most commonly used Inhibitors,research,lifescience,medical polymers are poly(D,L-lactic-co-glycolic) acid (PLGA) and its derivates (Figure 3), due to their inherent advantages over other systems. They are biodegradable and biocompatible, are able to release molecules during long periods of time (weeks or months), and they are ease to administer via injection [59] or orally [60]. In addition, Inhibitors,research,lifescience,medical PLGA has been approved for human use in sutures [61], bone implants [62], and screws [63] as well as in implants for sustained drug delivery [64]. Apart from PLGA, other polymers have also been used for vaccination purposes, such as alginate

[65], chitin [66], albumin [67], sodium polyacrylate [68], chitosan [69], poly-ε-caprolactone [70], or poly(γ-glutamic acid) [71] as well as some polymer combinations [72, 73]. Figure 3 Scanning electron CYTH4 micrograph of PLGA microparticles (×10,000). In these formulations, the antigen can be either entrapped or adsorbed on the surface of the particles. The delivery of the antigen can be slow and continuous, by pulses or it can be triggered by external or environmental factors such as changes in the pH [74], temperature [75], ionic strength [76], or electric and magnetic fields [77]. The particle size and size distribution are important factors to determine antigen release rate, as the total surface area for protein delivery depends on the particle size [78].