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首页> 外文期刊>Vaccine >The choice of linker for conjugating R848 to inactivated influenza virus determines the stimulatory capacity for innate immune cells
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The choice of linker for conjugating R848 to inactivated influenza virus determines the stimulatory capacity for innate immune cells

机译：用于将R848结合到灭活的流感病毒的接头决定了先天免疫细胞的刺激能力

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摘要

Inactivated influenza vaccines are not approved for use in infants less than 6 months of age due to poor immunogenicity in that population. While the live attenuated influenza vaccine has the potential to be more immunogenic, it is not an option for infants and other vulnerable populations, including the elderly and immunocompromised individuals due to safety concerns. In an effort to improve the immunogenicity of the inactivated vaccine for use in vulnerable populations, we have used an approach of chemically crosslinking the Toll-like receptor (TLR) 7/8 agonist R848 directly to virus particles. We have reported previously that an R848-conjugated, inactivated vaccine is more effective at inducing adaptive immune responses and protecting against lung pathology in influenza challenged neonatal African green monkeys than is the unmodified counterpart. In the current study, we describe a second generation vaccine that utilizes an amide-sulfhydryl crosslinker with different spacer chemistry and length to couple R848 to virions. The new vaccine has significantly enhanced immunostimulatory activity for murine macrophages and importantly for monocyte derived human dendritic cells. Demonstration of the significant differences in stimulatory activity afforded by modest changes in linker impacts our fundamental view of the design of TLR agonist-antigen vaccines. (C) 2018 Elsevier Ltd. All rights reserved.
机译：由于人群中的免疫原性差，灭活的流感疫苗未被批准用于少于6个月的婴儿。虽然现场减毒的流感疫苗具有更具免疫原性的潜力，但它不是婴儿和其他弱势群体的选择，包括由于安全问题为老年和免疫功能的人。努力改善灭活疫苗的免疫原性用于弱势群体，我们已经使用了将Toll样受体（TLR）7/8激动剂R848的方法与病毒颗粒化学交联的方法。我们以前报道了R848缀合的灭活疫苗在诱导适应性免疫应答和肺病中的肺病理学中的攻击挑战性新生儿非洲绿色猴子比是未修改的对应物更有效。在目前的研究中，我们描述了一种第二代疫苗，其利用具有不同间隔化学和长度的酰胺 - 巯基交联剂和长度耦合到病毒粒子。新疫苗显着增强了鼠巨噬细胞的免疫刺激活性，并且重要的是对于单核细胞衍生的人树突细胞。通过适度的接头变化提供了刺激活动的显着差异影响了我们对TLR激动剂 - 抗原疫苗设计的基本观。 （c）2018年elestvier有限公司保留所有权利。

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