期刊
ACS NANO
卷 13, 期 12, 页码 13809-13817出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b04071
关键词
polymer/lipid nanoparticles; systemic and gastrointestinal immunity; all-trans retinoic acid; CpG-ODN; lymph-node-amplifying effect
类别
资金
- Pilot Project of Chinese Academy of Sciences [XDB29040303]
- Foundation for Innovative Research Groups of the National Natural Science Foundation of China [21821005]
- National Natural Science Foundation of China [21776287, 21576268, 21778023, 21908229]
- Program of Introducing Talents of Discipline to Universities [111-2-06]
- National First-class Discipline Program of Light Industry Technology and Engineering [LITE2018-015]
- Chinese Academy of Sciences [ZDBS-LY-SLH040]
- Open Funding Project of the State Key Laboratory of Biochemical Engineering [2014KF-02]
Parenteral vaccinations are not able to elicit effective systemic and gastrointestinal immune protection simultaneously because the lymphocytes are typically restricted to primed tissues. Although all-trans retinoic acid (atRA) was reported to trigger the gut-homing of immunocytes, the bioavailability and systemic immune responses remain limited for use in robust enteric vaccinations. Here, we show that co-delivery of atRA, CpG oligodeoxynucleotides (CpG), and antigens via engineered polymer/lipid nanoparticles (PLNPs) could exploit the amplifying function of draining lymph nodes (DLNs) for potent gut tropism and immune activations. After intramuscular injection, forming an immune-potentiated environment at the injection site, the PLNPs induced the designated transfer of primed dendritic cells (DCs) to the DLNs instead of the gastrointestinal tissues. Within the DLNs, the immune-potentiated environment markedly amplified the antigen presentation and homing receptor switch among immunocytes, which simultaneously stimulated the preferential dissipation of activated lymphocytes in the peripheral and gastrointestinal tissues, that is, exerted a DLN-amplifying effect. Compared with current atRA-containing formulations, the PLNPs not only boosted potent IgG secretions and T cell activations in the peripheral tissue but also provoked robust T cell homing and antigen-specific IgA levels in the gastrointestinal tracts in both ovalbumin and EV71 vaccinations. These data indicate that exploiting DLN amplification can stimulate potent systemic and gastrointestinal responses for more efficient enteric vaccinations.
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