Future Vaccine Manufacturing Hub: Advancing the manufacture and deployment of cost effective vaccines

未来疫苗制造中心：推进具有成本效益的疫苗的制造和部署

基本信息

批准号：
EP/R013764/1
负责人：
Robin Shattock
金额：
$ 1599.37万
依托单位：
Imperial College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FR013764%2F1
关键词：
Future Vaccine Manufacturing Hub Advancing

项目摘要

Vaccine manufacturing systems have undergone evolutionary optimisation over the last 60 years, with occasional disruptions due to new technology (e.g. mammalian cell cultures replacing egg-based systems for seasonal influenza vaccine manufacture). Global vaccination programmes have been a great success but the production and distribution systems from vaccines still suffer from costs associated with producing and purifying vaccines and the need to store them between 2 and 8 degrees C. This can be a challenge in the rural parts of low and middle income countries where 24 million children do not have access to appropriate vaccinations every year. An additional challenge is the need to rapidly respond to new threats, such as the Ebola and Zika viruses, that continue to emerge. The development of a "first responder" strategy for the latter means that there are two different types of challenges that future vaccine manufacturing systems will have to overcome: 1. How to design a flexible modular production system, that once a new threat is identified and sequenced, can switch into manufacturing mode and produce of the order of 10,000 doses in a matter of weeks as part of localised containment strategy? 2. How to improve and optimise existing manufacturing processes and change the way vaccines are manufactured, stabilised and stored so that costs are reduced, efficiencies increased and existing and new diseases prevented effectively? Our proposed programme has been developed with LMIC partners as an integrated approach that will bring quick wins to challenge 2 while building on new developments in life sciences, immunology and process systems to bring concepts addressing challenge 1 to fruition.Examples of strategies for challenge 1 are RNA vaccines. The significant advantage of synthetic RNA vaccines is the ability to rapidly manufacture many thousands of doses within a matter of weeks. This provides a viable business model not applicable to other technologies with much longer lag phases for production (viral vectors, mammalian cell culture), whereby procurement of the vaccine can be made on a needs basis avoiding the associated costs of stockpiling vaccines for rapid deployment, monitoring their on going stability and implementing a cycle of replacement of expired stock. In addition, low infrastructure and equipment costs make it feasible to establish manufacture in low-income settings, where all required equipment has potential to be run from a generator driven electrical supply in the event of power shortage. This fits the concept of a distributed, flexible platform technology, in that once a threat is identified, the specific genetic code can be provided to the manufacturing process and the doses of the specific vaccine can be produced without delay. Additional concepts that we will explore in this category include the rapid production of yeast and bacterially expressed particles that mimic membrane expressed components of pathogenic viruses and bacteria.Examples of strategies for challenge 2 build on our work on protein stabilisation which has been shown to preserve the function of delicate protein enzymes at temperatures over 100 degrees C. We shall exploit this knowledge to develop new vaccine stabilisation and formulation platforms. These can be used in two ways: (a) to support the last few miles of delivery from centralised cold chains to patients through reformulation and (b) for direct production of thermally stable forms, i.e. vaccines that retain their activity for months despite being not being refrigerated. We believe that the best way to deliver these step changes in capability and performance is through a team-based approach that applies deep integration in two dimensions: between UK and LMIC partners to ensure that all the LMIC considerations are "baked in" from the start and between different disciplines accounting for the different expertise that will be required to meet the challenges.

在过去的60年中，疫苗制造系统经过了进化优化，由于新技术而偶尔会受到干扰（例如，哺乳动物细胞培养物取代基于鸡蛋的系统用于季节性流感疫苗生产）。全球疫苗接种计划取得了巨大的成功，但是疫苗的生产和分配系统仍然遭受与生产和净化疫苗相关的成本，并且需要将它们存储在2至8度之间。在2400万儿童无法获得适当的疫苗接种的低水平和中等国家的农村地区，这可能是一个挑战。另一个挑战是需要快速应对继续出现的新威胁，例如埃博拉病毒和寨卡病毒。对后者的“第一响应者”策略的制定意味着未来疫苗制造系统必须克服两种不同类型的挑战：1。如何设计柔性模块化生产系统，一旦确定和测序了新的威胁，就可以在本地化的策略中转变为10,000剂剂量的制造方式和10,000剂剂量的制造模式和产量？ 2.如何改善和优化现有的制造过程，并改变疫苗的制造，稳定和存储方式，以降低成本，效率提高，现有和新疾病有效地阻止了？我们提出的计划是与LMIC合作伙伴一起开发的，作为一种综合方法，它将在基于生命科学的新发展，免疫学和流程系统的基础上挑战2，以使挑战1的概念为实现。挑战策略1是RNA疫苗。合成RNA疫苗的显着优势是能够在几周内快速生产数千剂。这提供了一种可行的业务模型，不适用于其他技术的生产滞后阶段更长的技术（病毒载体，哺乳动物细胞培养），从而可以根据需要进行疫苗的采购，以避免避免库存疫苗的相关成本以快速部署，从而监控其进行稳定并实施经过经验的库存循环。此外，低基础设施和设备成本使在低收入设置中建立生产是可行的，在电源短缺的情况下，所有必需的设备都有可能从发电机驱动的电源运行。这符合分布式灵活的平台技术的概念，因为一旦确定了威胁，就可以向制造过程提供特定的遗传代码，并且可以毫不延迟生产特定疫苗的剂量。我们将在此类别中探索的其他概念包括模仿膜表达病原病毒和细菌组成部分的酵母和细菌表达的颗粒。这些可以通过两种方式使用：（a）通过重新制定从集中式冷链到患者的最后几英里，以及（b）直接生产热稳定形式，即尽管没有被冷藏，但仍保留了数月的活动的疫苗。我们认为，实现能力和性能的这些步骤变化的最佳方法是通过基于团队的方法来实现二维的深入集成：在英国和LMIC合作伙伴之间，以确保从一开始和不同学科之间“烘烤”所有LMIC考虑因素，而不同的学科涉及不同的专业知识，这将需要应对挑战。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Polymer Microarrays Rapidly Identify Competitive Adsorbents of Virus-like Particles (VLPs)

聚合物微阵列快速识别病毒样颗粒 (VLP) 的竞争性吸附剂

DOI：
10.26434/chemrxiv.12966725
发表时间：
2020
期刊：
影响因子：
0
作者：
Alexander M
通讯作者：
Alexander M

Precisely targeted gene delivery in human skin using supramolecular cationic glycopolymers

DOI：
10.1039/d0py00449a
发表时间：
2020-06-14
期刊：
POLYMER CHEMISTRY
影响因子：
4.6
作者：
Blakney, Anna K.;Liu, Renjie;Becer, C. Remzi
通讯作者：
Becer, C. Remzi

The SARS-CoV-2 spike protein: balancing stability and infectivity.

DOI：
10.1038/s41422-020-00430-4
发表时间：
2020-12
期刊：
Cell research
影响因子：
44.1
作者：
Berger I;Schaffitzel C
通讯作者：
Schaffitzel C

Oxygen-Tolerant RAFT Polymerization Initiated by Living Bacteria.

DOI：
10.1021/acsmacrolett.2c00372
发表时间：
2022-08-16
期刊：
ACS MACRO LETTERS
影响因子：
7.015
作者：
Bennett, Mechelle R.;Moloney, Cara;Catrambone, Francesco;Turco, Federico;Myers, Benjamin;Kovacs, Katalin;Hill, Philip J.;Alexander, Cameron;Rawson, Frankie J.;Gurnani, Pratik
通讯作者：
Gurnani, Pratik

Investigating histidinylated highly branched poly(lysine) for siRNA delivery.

研究用于 siRNA 递送的组氨酸化高度支化聚赖氨酸。