Nanovaccines Mediated Subcutis-to-Intestine Cascade for Improved Protection against Intestinal Infections

SMALL(2022)

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摘要
Parenteral vaccines typically can prime systemic humoral immune response, but with limited effects on cellular and mucosal immunity. Here, a subcutis-to-intestine cascade for navigating nanovaccines to address this limitation is proposed. This five-step cascade includes lymph nodes targeting, uptaken by dendritic cells (DCs), cross-presentation of antigens, increasing CCR9 expression on DCs, and driving CD103(+) DCs to mesenteric lymph nodes, in short, the LUCID cascade. Specifically, mesoporous silica nanoparticles are encapsulated with antigen and adjuvant toll-like receptor 9 agonist cytosine-phosphate-guanine oligodeoxynucleotides, and further coated by a lipid bilayer containing all-trans retinoic acid. The fabricated nanovaccines efficiently process the LUCID cascade to dramatically augment cellular and mucosal immune responses. Importantly, after being vaccinated with Salmonella enterica serovar Typhimurium antigen-loaded nanovaccine, the mice generate protective immunity against challenge of S. Typhimurium. These findings reveal the efficacy of nanovaccines mediated subcutis-to-intestine cascade in simultaneously activating cellular and mucosal immune responses against mucosal infections.
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关键词
cellular immune responses, intestinal infections, mucosal immune responses, nanovaccines, subcutis-to-intestine cascade
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