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The PLGA particle size has been varied and surface modifications have been introduced into vaccine formulations for use in oral, mucosal, and systemic delivery. The sizes, surface modification, and release profiles of PLGA particles were shown to affect the immunogenicity of entrapped antigens. The average size of an aerosolized PLGA or poly(l-lactic acid)-based nanoparticle pulmonary hepatitis B virus vaccine PDGFRB formulation was suggested to influence the immunogenicity of the antigen [45]. Nanoparticles larger than 500?nm induced the generation of antigen-specific secretary IgA more effectively than smaller nanoparticles (PLX4032 chemical structure lipid coating of PLGA nanoparticles was shown to enhance the antigen-specific IgG titer values more than 10 folds. Other groups have conjugated a candidate P. vivax malaria antigen, VMP001, to the surfaces of lipid-coated PLGA particles, and MPL has been incorporated into the lipid membranes [47]. In the study PLGA particle surfaces were coated with lipids composed of DOPC, CT99021 DOPG, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide]. The prolonged release of antigens delivered by PLGA nanoparticles was shown to enhance the immune response to the model OVA antigen [8]. PLGA nanoparticles provided an OVA release profile that extended over 10 weeks and was much slower than the release profile obtained from a liposomal formulation. In line with the sustained release profile, an OVA�CPLGA particulate vaccine formulation induced a higher antibody titer compared to the liposome formulation 8 weeks after subcutaneous administration in mice. The synthetic PLGA vaccine SEL-068 (Selecta Bioscience, Inc., USA) is now in phase I clinical trials for the prevention of nicotine addiction and relapse (http://www.selectabio.com). SEL-068 was designed to facilitate smoking cessation and is the first nano-vaccine to enter clinical trials. The SEL-068 formulation incorporates a universal peptide antigen for eliciting T helper cell response and an immunostimulating TLR agonist into the PLGA polymer matrix. Nicotine, a B cell antigen, is covalently linked to the nanoparticle surfaces. No dose-limiting systemic toxicities were observed in a repeat-dose GLP safety and efficacy study in cynomolgus monkeys. Other biodegradable polymers, including poly (��-caprolactone) and polyanhydrides, have been tested for their utility in vaccine delivery applications. The H1N1 hemagglutinin antigen was incorporated into chitosan-coated polycaprolactone nanoparticles.