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Biomaterial vaccines capturing pathogen-associated molecular patterns protect against bacterial infections and septic shock
Nature Biomedical Engineering ( IF 26.8 ) Pub Date : 2021-07-08 , DOI: 10.1038/s41551-021-00756-3
Michael Super 1, 2 , Edward J Doherty 1 , Mark J Cartwright 1 , Benjamin T Seiler 1 , Fernanda Langellotto 1 , Nikolaos Dimitrakakis 1 , Des A White 1 , Alexander G Stafford 1 , Mohan Karkada 1 , Amanda R Graveline 1 , Caitlin L Horgan 1 , Kayla R Lightbown 1 , Frank R Urena 1 , Chyenne D Yeager 1 , Sami A Rifai 1 , Maxence O Dellacherie 3 , Aileen W Li 3 , Collin Leese-Thompson 1 , Hamza Ijaz 1 , Amanda R Jiang 2 , Vasanth Chandrasekhar 1 , Justin M Scott 1 , Shanda L Lightbown 1 , Donald E Ingber 1, 2, 3 , David J Mooney 1, 3
Affiliation  

Most bacterial vaccines work for a subset of bacterial strains or require the modification of the antigen or isolation of the pathogen before vaccine development. Here we report injectable biomaterial vaccines that trigger potent humoral and T-cell responses to bacterial antigens by recruiting, reprogramming and releasing dendritic cells. The vaccines are assembled from regulatorily approved products and consist of a scaffold with absorbed granulocyte-macrophage colony-stimulating factor and CpG-rich oligonucleotides incorporating superparamagnetic microbeads coated with the broad-spectrum opsonin Fc-mannose-binding lectin for the magnetic capture of pathogen-associated molecular patterns from inactivated bacterial-cell-wall lysates. The vaccines protect mice against skin infection with methicillin-resistant Staphylococcus aureus, mice and pigs against septic shock from a lethal Escherichia coli challenge and, when loaded with pathogen-associated molecular patterns isolated from infected animals, uninfected animals against a challenge with different E. coli serotypes. The strong immunogenicity and low incidence of adverse events, a modular manufacturing process, and the use of components compatible with current good manufacturing practice could make this vaccine technology suitable for responding to bacterial pandemics and biothreats.



中文翻译:

捕获病原体相关分子模式的生物材料疫苗可预防细菌感染和感染性休克

大多数细菌疫苗适用于细菌菌株的一个子集,或者在疫苗开发之前需要修改抗原或分离病原体。在这里,我们报告了可注射的生物材料疫苗,通​​过招募、重编程和释放树突状细胞,触发有效的体液和 T 细胞对细菌抗原的反应。这些疫苗由监管批准的产品组装而成,由一个支架组成,该支架具有吸收的粒细胞-巨噬细胞集落刺激因子和富含 CpG 的寡核苷酸,其中结合了涂有广谱调理素 Fc-甘露糖结合凝集素的超顺磁性微珠,用于磁性捕获病原体-来自灭活细菌细胞壁裂解物的相关分子模式。疫苗保护小鼠免受耐甲氧西林皮肤感染金黄色葡萄球菌、小鼠和猪抵抗来自致命大肠杆菌挑战的感染性休克,当加载从受感染动物身上分离的病原体相关分子模式时,未感染动物抵抗不同大肠杆菌血清型的挑战。强大的免疫原性和不良事件的低发生率、模块化的制造过程以及与当前良好制造实践兼容的组件的使用可以使这种疫苗技术适用于应对细菌大流行和生物威胁。

更新日期:2021-07-08
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