Double-metal ion adjuvant stabilized Pickering emulsion to amplify humoral and cellular immune responses  

作　　者：Zhaofei Guo Fuhua Wu Yanhua Xu Xue Tang Xiejin Xie Rui Hu Yangsen Ou Hongjiao Wei Lin Ye Chunting He Penghui He Hairui Wang Guangsheng Du Xun Sun 

机构地区：[1]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu 610041,China

出　　处：《Nano Research》2025年第3期360-371,共12页纳米研究(英文版)

基　　金：supported by the National Key Research and Development Program of China(No.2023YFC2307700);the National Natural Science Foundation of China(Nos.U24A20811 and 82341038);the Program Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System(No.SCCXTD-2025-18);the 111 project(No.B18035);the Fundamental Research Funds for the Central Universities.

摘　　要：Metal ions play critical roles in many immune processes,and their modulation may open up new forms of vaccine adjuvants.Current vaccines predominantly utilize aluminum salts as adjuvants,but alum has poor ability to induce cellular immunity.Manganese(Mn^(2+))can activate cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway for amplifying cellular immune responses,but free Mn^(2+)may cause certain neurotoxicity due to its random in vivo distribution.Herein,Mn^(2+)is initially biomineralized into human serum albumin nanoparticles(HSA-Mn)to improve the biocompatibility of Mn adjuvants.Then,HSA-Mn and alum adjuvants are co-dispersed at the squalene/water interphase,resulting in a bimetallic adjuvant co-stabilized Pickering nanoemulsion(HMANE).Compared to lecithin-stabilized emulsion,HMANE increased the surface roughness by approximately 6-fold and significantly improved its interactions with antigen-presenting cells(APCs).After vaccination,HMANE-adjuvanted inactivated SARS-CoV-2 virus(CorV-HMANE)rapidly induced antibody generation and efficiently activated the STING pathway to produce a stronger cellular immune response.In addition,the abundant memory B and T cells induced by the CorV-HMANE further ensured its long-term protective efficacy for at least 4 months.In conclusion,our study highlights the great potential of Pickering emulsions as metal adjuvant platforms,providing new insight for further adjuvant development.

关 键 词：Pickering nanoemulsion bimetallic adjuvant cGAS-STING vaccine 

分 类 号：R392[医药卫生—免疫学]