Biomaterial vaccines capturing pathogen-associated molecular patterns protect against bacterial infections and septic shock.
Biomaterial vaccines capturing pathogen-associated molecular patterns protect against bacterial infections and septic shock.
复制标题
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败血性休克。
DOI：
10.1038/s41551-021-00756-3
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发表时间：
2022
影响因子：
28.1
通讯作者：
Yeag
中科院分区：
文献类型：
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作者：
Super,Michael;Doherty,EdwardJ;Cartwright,MarkJ;Seiler,BenjaminT;Langellotto,Fernanda;Dimitrakakis,Nikolaos;White,DesA;Stafford,AlexanderG;Karkada,Mohan;Graveline,AmandaR;Horgan,CaitlinL;Lightbown,KaylaR;Urena,FrankR;Yeag
大多数细菌疫苗只对一部分细菌菌株有效，或者在研制疫苗前需要对抗原进行修饰或分离病原体。在这里，我们报道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，触发对细菌抗原的有效体液和t细胞反应。该疫苗由经监管部门批准的产品组装而成，由吸收的粒细胞-巨噬细胞集落刺激因子和富含cpg的寡核苷酸组成，其中含有包裹有广谱opsonin fc -甘露糖结合凝集素的超顺磁性微珠，用于从灭活细菌-细胞壁裂解物中磁性捕获病原体相关的分子模式。这些疫苗可以保护小鼠免受耐甲氧西林金黄色葡萄球菌的皮肤感染，保护小鼠和猪免受致命大肠杆菌攻击造成的感染性休克，并且当加载从受感染动物中分离出的病原体相关分子模式时，可以保护未受感染动物免受不同细菌的攻击。coliserotypes。该疫苗具有很强的免疫原性和较低的不良事件发生率，采用模块化生产工艺，使用符合现行良好生产规范的成分，可使该疫苗技术适用于应对细菌大流行和生物威胁。
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-resistantStaphylococcus aureus, mice and pigs against septic shock from a lethalEscherichia colichallenge and, when loaded with pathogen-associated molecular patterns isolated from infected animals, uninfected animals against a challenge with differentE. coliserotypes. 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.