Super Michael, Doherty Edward J, Cartwright Mark J, Seiler Benjamin T, Langellotto Fernanda, Dimitrakakis Nikolaos, White Des A, Stafford Alexander G, Karkada Mohan, Graveline Amanda R, Horgan Caitlin L, Lightbown Kayla R, Urena Frank R, Yeager Chyenne D, Rifai Sami A, Dellacherie Maxence O, Li Aileen W, Leese-Thompson Collin, Ijaz Hamza, Jiang Amanda R, Chandrasekhar Vasanth, Scott Justin M, Lightbown Shanda L, Ingber Donald E, Mooney David J
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Nat Biomed Eng. 2022 Jan;6(1):8-18. doi: 10.1038/s41551-021-00756-3. Epub 2021 Jul 8.
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.
大多数细菌疫苗仅对部分细菌菌株有效，或者在疫苗研发前需要对抗原进行修饰或分离病原体。在此，我们报告了一种可注射生物材料疫苗，该疫苗通过募集、重编程和释放树突状细胞，引发针对细菌抗原的强效体液免疫和T细胞免疫反应。这些疫苗由监管部门批准的产品组装而成，由一个支架组成，支架上吸附有粒细胞-巨噬细胞集落刺激因子和富含CpG的寡核苷酸，并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，用于从灭活的细菌细胞壁裂解物中磁性捕获病原体相关分子模式。这些疫苗可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死性大肠杆菌攻击引起的败血症休克，并且当装载从感染动物分离的病原体相关分子模式时，可保护未感染动物免受不同大肠杆菌血清型的攻击。这种疫苗技术具有强大的免疫原性、低不良事件发生率、模块化生产工艺以及使用符合现行良好生产规范的组件，可能使其适用于应对细菌大流行和生物威胁。
