New vaccine adjuvants from metal organic frameworks

金属有机框架的新型疫苗佐剂

• 批准号: EP/L020254/1
• 负责人: Gareth Williams
• 金额: $ 12.6万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FL020254%2F1
• 关键词: New; vaccine; adjuvants; metal; organic

Prophylactic vaccination is arguably the most effective medical intervention ever developed, saving some 3 million lives per year. A vaccine is a preparation that causes an individual to develop effective biological defence mechanisms (immunity) against a pathogen. Most often, vaccination is used to protect against an infectious disease, though cancers are also increasingly being targeted. Typically a vaccine will contain a small amount of a material which resembles a disease-causing agent (the 'antigen' - a viral, microbial or tumour component), but does not carry an infectious risk. The vaccine causes the immune system to recognize the antigen as foreign, eliminate it, and "remember" it, thereby conferring effective immunity against the pathogen. In order to ensure that robust immunity is inculcated, an "adjuvant" is usually added to vaccines to mimic the danger signals that naturally trigger immune responses. At present, inorganic compounds known as 'alums' (usually either AlOOH or amorphous aluminium hydroxyphosphate) are used as adjuvants in the majority of cases. 'Alum' can lead to strong immunity to microbes and larger parasites, but does not provoke the necessary immune response to overcome viral infections or the majority of cancers. There is at present a lack of alternative adjuvants able to drive such responses; in this work, we seek to redress this deficiency.Recent work has established that a family of inorganic materials known as layered double hydroxides can act as potent adjuvants whose immunogenicity can be systematically varied through control of their physicochemical properties. In this work, we will explore the metal organic framework (MOF) family of materials. MOFs are a class of materials containing metal centres connected in three dimensions by organic linkers. They have enormous structural diversity, and commonly contain empty 'pores' into which antigens may be incorporated. MOFs have successfully been used for drug delivery and other biomedical applications. They have however never been explored for use as adjuvants. We will systematically synthesise three sets of MOFs (known materials, known materials with immunogenic moieties embedded, and MOFs where the organic linker is immunogenic) and investigate the immune response to these in vitro. This work will be complemented with a detailed systems-level study looking to draw correlations between the materials' physicochemical properties and the immune responses they invoke.

预防性疫苗接种可以说是迄今为止最有效的医疗干预措施，每年挽救约 300 万人的生命。疫苗是一种使个体针对病原体形成有效的生物防御机制（免疫）的制剂。最常见的是，疫苗接种用于预防传染病，尽管癌症也越来越成为目标。通常，疫苗将含有少量类似于致病因子的物质（“抗原”——病毒、微生物或肿瘤成分），但不具有感染风险。疫苗使免疫系统将抗原识别为外来抗原，消除它，并“记住”它，从而赋予针对病原体的有效免疫力。为了确保灌输强大的免疫力，通常会在疫苗中添加“佐剂”来模仿自然触发免疫反应的危险信号。目前，在大多数情况下，被称为“明矾”的无机化合物（通常是AlOOH或无定形羟基磷酸铝）被用作佐剂。 “明矾”可以对微生物和较大的寄生虫产生强大的免疫力，但不会激发克服病毒感染或大多数癌症所需的免疫反应。目前缺乏能够驱动此类反应的替代佐剂；在这项工作中，我们试图弥补这一缺陷。最近的工作已经确定，一系列被称为层状双氢氧化物的无机材料可以充当有效的佐剂，其免疫原性可以通过控制其理化性质来系统地改变。在这项工作中，我们将探索金属有机骨架（MOF）系列材料。 MOF 是一类含有通过有机连接体在三个维度上连接的金属中心的材料。它们具有巨大的结构多样性，并且通常含有可以掺入抗原的空“孔”。 MOF 已成功用于药物输送和其他生物医学应用。然而，从未探索将它们用作佐剂。我们将系统地合成三组MOF（已知材料、嵌入免疫原性部分的已知材料以及有机连接子具有免疫原性的MOF）并研究体外对它们的免疫反应。这项工作将得到详细的系统级研究的补充，旨在绘制材料的物理化学性质和它们引起的免疫反应之间的相关性。

项目成果

The potential for a protective vaccine for rhinovirus infections.

鼻病毒感染保护性疫苗的潜力。

• DOI: 10.1586/14760584.2016.1142375
• 发表时间: 2016
• 期刊: Expert review of vaccines
• 影响因子: 6.2
• 作者: Williams GR