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J Control Release . A nano-adjuvant platform potentiates immunity for potent mucosal and systemic defense against influenza

tetano

Editor, Senior Moderator
J Control Release

. 2026 Sep 15:115353.
doi: 10.1016/j.jconrel.2026.115353. Online ahead of print.

A nano-adjuvant platform potentiates immunity for potent mucosal and systemic defense against influenza​


Hanghang Cheng 1 , Yanan Wang 2 , Siqiao Wang 3 , Zekun Meng 2 , Xueying Zhai 4 , Rongzhou Lv 2 , Anchun Cheng 5 , Kaifeng Guan 6 , Gaiping Zhang 7

Affiliations


Abstract​


Vaccines against respiratory viruses such as influenza require adjuvant platforms capable of simultaneously inducing robust mucosal and systemic immunity. Here, we report a PEGylated aluminum‑manganese oxide hybrid nano-adjuvant (Al-Mn-PEG) as an efficient mucosal vaccine delivery system. Al-Mn-PEG exhibits high stability and biocompatibility, enhancing antigen uptake, activation, and lysosomal escape in antigen-presenting cells, thus promoting cross-presentation. In vivo, intranasal immunization with Al-Mn-PEG loaded with hemagglutinin from influenza A or B viruses induces strong mucosal sIgA and systemic IgG responses, drives a mixed Th1/Th2 immune profile with systemic Th1 skewing, and activates CD8+ T cells, resulting in comprehensive immune protection. Mechanistically, Al-Mn-PEG engages both the STING/TBK1/IRF3 and NLRP3 pathways, which potentiate the immune system and drive coordinated innate and adaptive immune responses. This work establishes Al-Mn-PEG as a versatile adjuvant platform, offering a strategy for next-generation respiratory vaccines.

Keywords: Aluminum‑manganese oxides; Cross-presentation; Influenza; Lysosomal escape; Modulate the immune system; Mucosal vaccines.
 
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