Nature2014-06-24 2:51 PM

以淋巴结为目标的“亚单元”疫苗 Structure-based programming of lymph-node targeting in molecular vaccines

论文摘要 

基于纯化的肽、蛋白或多糖的疫苗,再加上设计用来促进免疫反应的分子辅药,比替代品在制造上可能更安全、更容易。然而,一般来说这种“亚单元”疫苗比那些采用活减毒病原体的疫苗诱发的免疫反应较弱。Darrell Irvine及同事为非肠道注射后“亚单元”疫苗向淋巴器官的分子定向演示了一个简单的化学策略。他们设计了一种两亲疫苗,由连接到一个亲脂尾巴上的一个肽抗原或一个辅药货物组成。所获得的CpG-DNA/肽两亲疫苗与母体化合物相比抗肿瘤效果有实质性增强,而毒性却有所降低。

Abstract 

In cancer patients, visual identification of sentinel lymph nodes (LNs) is achieved by the injection of dyes that bind avidly to endogenous albumin, targeting these compounds to LNs, where they are efficiently filtered by resident phagocytes. Here we translate this ‘albumin hitchhiking’ approach to molecular vaccines, through the synthesis of amphiphiles (amph-vaccines) comprising an antigen or adjuvant cargo linked to a lipophilic albumin-binding tail by a solubility-promoting polar polymer chain. Administration of structurally optimized CpG-DNA/peptide amph-vaccines in mice resulted in marked increases in LN accumulation and decreased systemic dissemination relative to their parent compounds, leading to 30-fold increases in T-cell priming and enhanced anti-tumour efficacy while greatly reducing systemic toxicity. Amph-vaccines provide a simple, broadly applicable strategy to simultaneously increase the potency and safety of subunit vaccines.

KEYWORDS

SHARE & LIKE

COMMENTS

ABOUT THE AUTHOR

Nature

Nature Magazine

0 Following 27 Fans 0 Projects 626 Articles

SIMILAR ARTICLES

Meristems encompass stem/progenitor cells that sustain postembryonic growth of all plant organs. How meristems are activated and sustained by nutrient

Read More

Transcription of ribosomal RNA by RNA polymerase (Pol) I initiates ribosome biogenesis and regulates eukaryotic cell growth. The crystal structure of P

Read More

Abstract The effect of anthropogenic aerosols on cloud droplet concentrations and radiative properties is the source of one of the largest uncertainti

Read More

Abstract Ecological and societal disruptions by modern climate change are critically determined by the time frame over which climates shift beyond his

Read More

Abstract Evidence from Greenland ice cores shows that year-to-year temperature variability was probably higher in some past cold periods, but there is

Read More

Abstract The land and ocean act as a sink for fossil-fuel emissions, thereby slowing the rise of atmospheric carbon dioxide concentrations1. Although t

Read More

论文摘要 人们已经非常清楚生物多样性对初级生产力等生态系统功能有一个积极影响,但它对植物凋落物的多样性和分解植物凋落物的生物的多样性的影响却不是很清楚。Stephan H?ttenschwiler及同事对从亚北极到热带、包括水生生态系统和陆地生态系统在内的五个地点所进行的并行操纵实验中的凋落物多样性进

Read More

论文摘要 FANTOM5 (即“哺乳动物基因组-5的功能注解”) 是一个大型国际合作项目的第5大阶段,其目标是分析定义每个人类细胞类型的转录调控网络。本期Nature上的两篇Articles论文发表了该项目的一些最新结果。第一篇论文利用FANTOM5项目组的组织和原代细胞样本来定义整个人体中活性的、在

Read More

论文摘要 有证据表明,血管 (尤其是它们的内皮细胞) 控制器官的生长、平衡和再生。在本期Nature上发表的两篇论文中,Ralf Adams及同事证明,骨头血管含有专门支持骨成熟和再生的内皮细胞。Anjali Kusumbe等人在小鼠骨骼系统内识别出一个在介导骨生长中起关键作用的毛细血管亚型。这些血管

Read More

论文摘要 CD4 T细胞(携带能够识别被病毒感染的细胞表面上的CD4抗原的受体的辅助T细胞)的丧失是艾滋病发病的根源。在这项研究中,Warner Greene等人识别出静止的淋巴CD4 T细胞在HIV感染过程中被耗尽的机制。利用保持了天然淋巴环境的人淋巴组织的体外培养,本文作者发现,失败的病毒复制触发

Read More