New vaccine adjuvants from metal organic frameworks

预防性疫苗接种可以说是有史以来最有效的医疗干预措施，每年可挽救约300万人的生命。疫苗是一种制剂，可使个体对病原体产生有效的生物防御机制（免疫）。大多数情况下，接种疫苗是为了预防传染病，尽管癌症也越来越多地成为目标。通常情况下，疫苗将含有少量类似于致病因子的物质（“抗原”——一种病毒、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物，将其清除并“记住”它，从而赋予对病原体的有效免疫力。为了确保接种强大的免疫力，通常在疫苗中添加一种“佐剂”，以模拟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或无定形的羟基磷酸铝）被用作佐剂。“明矾”可以导致对微生物和较大寄生虫的强大免疫力，但不会引发克服病毒感染或大多数癌症所需的免疫反应。目前缺乏能够驱动这种反应的替代佐剂；在这项工作中，我们试图纠正这一缺陷。最近的研究表明，一种被称为层状双氢氧化物的无机材料家族可以作为有效的佐剂，其免疫原性可以通过控制其物理化学性质而系统地改变。在这项工作中，我们将探索金属有机框架（MOF）材料家族。mof是一类包含金属中心的材料，通过有机连接件在三维空间中连接。它们具有巨大的结构多样性，通常含有空的“孔”，抗原可以被纳入其中。mof已成功地用于药物输送和其他生物医学应用。然而，它们从未被用作佐剂。我们将系统地合成三组mof（已知材料，嵌入免疫原性片段的已知材料，以及有机连接物具有免疫原性的mof），并在体外研究对这些mof的免疫反应。这项工作将辅以一项详细的系统级研究，旨在绘制材料的物理化学性质与其引发的免疫反应之间的相关性。

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.