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Improved vaccine-induced immune responses via a ROS-triggered nanoparticle-based antigen delivery system


Subunit vaccines that are designed based on recombinant antigens or peptides have shown promising potential as viable substitutes for traditional vaccines due to their better safety and specificity. However, induction of adequate in vivo immune responses with appropriate effectiveness remains a major challenge for vaccine development. More recently, implementation of nanoparticle-based antigen delivery system has been considered a promising approach to improve in vivo efficacy for subunit vaccine development. Thus, we have designed and prepared a nanoparticle-based antigen delivery system composed of three-armed PLGA, which is conjugated to PEG via the peroxalate ester bond (3s-PLGA-PO-PEG) and PEI as a cationic adjuvant (PPO NPs). It has been known that during foreign pathogen attack, NADPH, an oxidase, of the host organisms is activated and generates elevated level of reactive oxygen species, hydrogen peroxide (H2O2) primarily, as a defensive mechanism. Considering the sensitivity of the peroxalate ester bond to H2O2 and the cationic property of PEI for the induction of immune responses, this 3s-PLGA-PO-PEG/PEI antigen delivery system is expected to be both ROS responsive and facilitative in antigen uptake without severe toxicity that has been reported with cationic adjuvants. Indeed, our results demonstrated excellent loading capacity and in vitro stability of the PPO NPs encapsulated with model antigen, ovalbumin(OVA). Co-culturing of bone marrow dendritic cells with the PPO NPs also led to enhanced dendritic cell maturation, antigen uptake, enhanced lysosomal escape, antigen cross-presentation and in vitro CD8+ T cell activation. In vivo experiments using mice further revealed that administration of the PPO nanovaccine induced robust OVA-specific antibody production, upregulation of splenic CD4+ and CD8+ T cell proportions as well as increase in memory T cells generation. In summary, we report here a ROS-triggered nanoparticle-based antigen delivery system that could be employed to promote in vivo efficacy of vaccine-induced immune responses.

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Publication details

The article was received on 14 Jan 2018, accepted on 12 Mar 2018 and first published on 12 Mar 2018

Article type: Paper
DOI: 10.1039/C8NR00355F
Citation: Nanoscale, 2018, Accepted Manuscript
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    Improved vaccine-induced immune responses via a ROS-triggered nanoparticle-based antigen delivery system

    X. Liang, J. Duan, X. Li, X. Zhu, Y. Chen, X. Wang, H. Sun, D. Kong, C. Li and J. Yang, Nanoscale, 2018, Accepted Manuscript , DOI: 10.1039/C8NR00355F

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