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Alpha-D-glucan nanoparticulate adjuvant induces a transient inflammatory response at the injection site and targets antigen to migratory dendritic cells.

ABSTRACT: Biodegradable nanoparticles with functionalized surfaces are attractive candidates as vaccine adjuvants. Nano-11 are cationic dendrimer-like ?-D-glucan nanoparticles with a diameter of 70-80?nm. Mice injected with antigen formulated with Nano-11 developed antibody titers that were similar or greater than antigen with aluminum adjuvant. Utilizing an in vivo imaging system, Nano-11 was shown to remain at the injection site after administration and cleared gradually over the course of 3 weeks. Injection of Nano-11 induced a transient inflammatory response characterized by recruitment of a mixed population of inflammatory cells, predominantly monocytes and macrophages with relatively few neutrophils. Recruited Mac-2+macrophages efficiently phagocytized the majority of Nano-11 at the injection site. Fluorescently labeled Nano-11 was present in cells in the draining lymph nodes 1 day after injection, with the majority contained in migratory dendritic cells. Injection of ovalbumin adsorbed to Nano-11 resulted in an increase of ovalbumin-containing cells in draining lymph nodes. Nano-11 delivered more antigen to antigen-presenting cells on a per cell basis and demonstrated more specific targeting to highly immunopotentiating migratory dendritic cells compared with soluble or aluminum hydroxide adsorbed ovalbumin. These results support the efficacy of Nano-11 and its potential use as a next generation vaccine adjuvant.

SUBMITTER: Lu F

PROVIDER: S-EPMC5627279 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Alpha-D-glucan nanoparticulate adjuvant induces a transient inflammatory response at the injection site and targets antigen to migratory dendritic cells.

Lu Fangjia F Mosley Yung-Yi C YC Rodriguez Rosales Randol J RJ Carmichael Brooke E BE Elesela Srikanth S Yao Yuan Y HogenEsch Harm H

NPJ vaccines 20170223

Biodegradable nanoparticles with functionalized surfaces are attractive candidates as vaccine adjuvants. Nano-11 are cationic dendrimer-like <i>α</i>-D-glucan nanoparticles with a diameter of 70-80 nm. Mice injected with antigen formulated with Nano-11 developed antibody titers that were similar or greater than antigen with aluminum adjuvant. Utilizing an in vivo imaging system, Nano-11 was shown to remain at the injection site after administration and cleared gradually over the course of 3 week ...[more]

PMID: 29263865

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Project description:MF59 is an oil-in-water emulsion adjuvant approved for human influenza vaccination in European Union. The mode of action of MF59 is not fully elucidated yet, but results from several years of investigation indicate that MF59 establishes an immunocompetent environment at injection site which promotes recruitment of immune cells, including antigen presenting cells (APCs), that are facilitated to engulf antigen and transport it to draining lymph node (dLN) where the antigen is accumulated. In vitro studies showed that MF59 promotes the differentiation of monocytes to dendritic cells (Mo-DCs). Since after immunization with MF59, monocytes are rapidly recruited both at the injection site and in dLN and appear to have a morphological change toward a DC-like phenotype, we asked whether MF59 could play a role in inducing differentiation of Mo-DC in vivo. To address this question we immunized mice with the auto-fluorescent protein Phycoerythrin (PE) as model antigen, in presence or absence of MF59. We measured the APC phenotype and their antigen uptake within dLNs, the antigen distribution within the dLN compartments and the humoral response to PE. In addition, using Ovalbumin as model antigen, we measured the capacity of dLN APCs to induce antigen-specific CD4 T cell proliferation. Here, we show, for the first time, that MF59 promotes differentiation of Mo-DCs within dLNs from intranodal recruited monocytes and we suggest that this differentiation could take place in the medullary compartment of the LN. In addition we show that the Mo-DC subset represents the major source of antigen-loaded and activated APCs within the dLN when immunizing with MF59. Interestingly, this finding correlates with the enhanced triggering of antigen-specific CD4 T cell response induced by LN APCs. This study therefore demonstrates that MF59 is able to promote an immunocompetent environment also directly within the dLN, offering a novel insight on the mechanism of action of vaccine adjuvants based on emulsions.

Dataset Information

Alpha-D-glucan nanoparticulate adjuvant induces a transient inflammatory response at the injection site and targets antigen to migratory dendritic cells.

Publications

Alpha-D-glucan nanoparticulate adjuvant induces a transient inflammatory response at the injection site and targets antigen to migratory dendritic cells.

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