Apoferritin as a virus-like particle for the display of multiple virulence factors for vaccine development

脱铁铁蛋白作为病毒样颗粒，用于展示疫苗开发的多种毒力因子

• 批准号: BB/M018741/1
• 负责人: Neil Thomas
• 金额: $ 19.02万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM018741%2F1
• 关键词: Apoferritin; virus; like; particle; display

Vaccines provide an efficient, cost effective method of protecting animals and humans against a large range of pathogens and avoid the need for large scale use of antibiotics and antiviral agents. This reduces the quantities of drugs used to treat infected cattle and minimizes the drug residues and metabolites that can subsequently appear in foodstuffs such as meat, milk or other dairy products. Since the time of Edward Jenner, vaccines have used either whole active benign viruses such as cowpox virus for protection against smallpox infections or chemically or heat-treated pathogenic viruses or bacteria that are unable to replicate/reproduce but produce a protective immune response in the animal being vaccinated. Provided the vaccines are correctly prepared and the virus/pathogen is completely deactivated, this approach works for a number of diseases, but for pathogens such as the influenza virus that rapidly mutates it is necessary to prepare new complex vaccines on an annual basis in order to ensure that the pathogen has not mutated such that it can evade the immune system. In order to make more efficient protective vaccines, researchers have moved away from using deactivated whole pathogens, preferring to generate vaccines based on unique proteins and sugars in them that stimulate both a humoral and cellular immune response. In order to be most effective these structures need to be presented to the immune system in multiple copies on nanoparticles ideally 10-40 nm in diameter and either several different proteins from a single pathogen or several different mutants of the same proteins from a single pathogen need to be presented to the immune system to counteract the changes in the pathogen over time. To achieve this researchers have examined a number of virus and other naturally occurring types of protein capsules and several human vaccines have been generated from these including ones against hepatitis and papillomavirus. We are proposing to use apoferritin as the nanoparticle as it can be produced in large quantities quickly and cheaply with a wide range of pathogen proteins attached. Because apoferritin can self-assemble in to a highly organised protein capsule by changing the pH of the solution, it can be developed into a modular system where large combinations of different antigens can be combined rapidly to generate nanoparticles suitable for vaccination. This would allow new vaccines to be generated rapidly in response to quickly evolving pathogens. To demonstrate the technology we will produce apoferritin-complexes which display proteins from bacteria involved in mastitis infections in cows and goats. Currently in the UK the dairy industry loses milk production equivalent to that of 120,000 cows per year due to mastitis and therefore eradicating this disease would reduce herd sizes freeing up both the land they occupy and the land required to produce their feed for alternative agriculture use. This would also significantly reduce the bovine carbon dioxide generation of the UK.The apoferritin technology could be widely exploited to develop a range of vaccines for both animal and human health.

疫苗提供了一种有效的、具有成本效益的方法来保护动物和人类免受多种病原体的侵袭，并避免了大规模使用抗生素和抗病毒药物的需要。这减少了用于治疗受感染牛的药物的数量，并最大限度地减少了随后可能出现在肉类、牛奶或其他乳制品等食品中的药物残留和代谢物。自Edward Jenner时代以来，疫苗要么使用完整的活性良性病毒(如牛痘病毒)来预防天花感染，要么使用化学或热处理的致病病毒，或者使用不能复制/繁殖但在被接种动物中产生保护性免疫反应的细菌。如果疫苗准备正确，病毒/病原体完全灭活，这种方法对一些疾病有效，但对于快速变异的病原体，如流感病毒，有必要每年准备新的复杂疫苗，以确保病原体没有变异，以至于它可以逃避免疫系统。为了制造更有效的保护性疫苗，研究人员已经不再使用灭活的整个病原体，而是更喜欢基于它们中独特的蛋白质和糖来产生疫苗，这种疫苗既能刺激体液免疫反应，也能刺激细胞免疫反应。为了最有效，这些结构需要以多个拷贝的纳米颗粒呈现给免疫系统，最好是直径10-40 nm，并且需要将来自单一病原体的几个不同蛋白质或来自单一病原体的相同蛋白质的几个不同突变体呈现给免疫系统，以抵消随着时间的推移病原体的变化。为了实现这一点，研究人员检查了一些病毒和其他自然产生的蛋白质胶囊，并从这些胶囊中产生了几种人类疫苗，包括针对肝炎和乳头瘤病毒的疫苗。我们建议使用载脂蛋白作为纳米颗粒，因为它可以大量、快速和廉价地生产，并附着广泛的病原体蛋白。由于载脂蛋白可以通过改变溶液的pH值自组装成高度组织化的蛋白质胶囊，它可以被开发成一个模块化系统，在这个系统中，不同抗原的大组合可以迅速结合起来，产生适合疫苗接种的纳米颗粒。这将使新疫苗能够迅速产生，以应对快速进化的病原体。为了演示这项技术，我们将生产脱铁蛋白复合体，它展示了与奶牛和山羊乳房炎感染有关的细菌的蛋白质。目前，在英国，由于乳房炎，奶制品行业每年损失相当于12万头奶牛的牛奶产量，因此根除这种疾病将减少牛群规模，释放它们占用的土地和生产饲料用于替代农业用途所需的土地。这也将大大减少英国牛二氧化碳的产生。载脂蛋白技术可以被广泛利用来开发一系列对动物和人类健康都适用的疫苗。

项目成果

Near-infrared PbS quantum dots functionalized with affibodies and ZnPP for targeted imaging and therapeutic applications

• DOI: 10.1088/2632-959x/ac33b8
• 发表时间: 2021-12-01
• 期刊: NANO EXPRESS
• 影响因子: 3
• 作者: Al-Ani, Ali W.;Zamberlan, Francesco;Turyanska, Lyudmila
• 通讯作者: Turyanska, Lyudmila