佐剂
抗原
乳铁蛋白
化学
免疫原性
病毒学
生物
免疫学
生物化学
作者
Jiexin Li,Qian Qiu,He Ren,Jingyu Zhang,Chen Zhang,Gengqi Liu,Boyang Sun,Baisong Zheng,Jonathan F. Lovell,Yumiao Zhang
出处
期刊:Nano Today
[Elsevier]
日期:2024-04-01
卷期号:55: 102156-102156
标识
DOI:10.1016/j.nantod.2024.102156
摘要
Co-delivery of antigens and adjuvants in a nanoparticle format could be beneficial for subunit vaccine development. Herein, we develop a nanovaccine comprising lactoferrin-Mn-PEG-diABZI-2-antigen, termed LaMP-A-antigen. Featuring a metalloprotein core, LaMP securely localizes manganese (Mn) in confined spaces formed by lactoferrin-PEG conjugates. LaMP efficiently coordinates imidazole-containing adjuvants (diABZI-2), yielding LaMP-A, which is subsequently functionalized by numerous his-tagged viral-derived antigenic proteins or peptides by simple admixture. Compared to regular metal chelation, LaMP-A-antigen is more physiologically stable and can be lyophilized and stored at room temperature without change in physical and immunological properties for months. Following screening of ten common metal ions, manganese and cobalt are found to enhance the adjuvant effect of diABZI-2 by activation of stimulator of interferon genes (STING). In particular, Mn2+ achieves a 39-fold adjuvant dose sparing effect. When the SARS-CoV-2 receptor-binding domain (RBD) is used as a model antigen, immunization with LaMP-A-RBD elicits strong mucosal, humoral and cellular immunity. Following a single intranasal administration of LaMP-A-RBD in hamsters, antigen-specific T cells as well as natural killer (NK) cells are induced, along with RBD-specific IgG and secretory IgA (sIgA), leading to rapid neutralization in a reporter pseudovirus challenge. Thus, the LaMP-A system represents a novel vaccine adjuvant system that displays antigens, and exploits metalloimmune responses via the cGAS-STING pathway to improve vaccine immunogenicity.
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