One-step and scalable manufacture of lymphatic - targeting liposomal vaccines
淋巴靶向脂质体疫苗的一步式、规模化生产
基本信息
- 批准号:2130201
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:英国
- 项目类别:Studentship
- 财政年份:2018
- 资助国家:英国
- 起止时间:2018 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Background. Vaccines are the most powerful and cost-effective way to prevent infectious diseases. Yet, global access to vaccines continues to face notable barriers: it is estimated that 19.4 million infants worldwide are still missing out on basic vaccines. To address this, an uninterrupted supply of high-quality vaccines, from manufacturer to recipient, is needed. Currently this supply chain is hindered by a range of factors including insufficient vaccine supply and limited local capacity to store, handle and administer vaccines as many require refrigeration. Therefore, agility in the supply chain combined with the development of effective and thermostable vaccine systems is required. A wide range of studies has shown that liposomes act as suitable adjuvants for vaccine antigens. Indeed, work from the project collaborative team has demonstrated that we can control liposomal physicochemical attributes (including size, charge and bilayer rigidity and composition) to enhance adjuvant efficacy [1]. Therefore, by exploiting liposomes we are able to reduce the amount of antigen required to produce effective vaccines and hence enhance vaccine yield. We can thus use these nanoparticles to deliver economical efficiencies in vaccine manufacture and drive down their cost and time of manufacture. In addition to their adjuvant properties, the applicants have also demonstrated that by incorporating antigen within these bilayer nanoparticles, protein antigens can be stabilised. Thus, liposomes could offer the potential to circumvent the need for cold-chain supply of vaccines and improve local capacity and supply. However, liposomal vaccines are complex formulations that require new manufacturing solutions to allow affordable and geographical access. To address this, we will build on our previous successful collaboration [2] and use novel microfluidic processes to manufacture complex formulations which will enhance vaccine efficacy. Thus we will address their manufacturing requirements both at the bedside and through scalable continuous manufacturing. To promote dose-sparing opportunities in vaccine formulation, this project will develop lymphatic-targeting vaccines. Normally, after injection, approximately 50 % of the injected dose of liposomes clears from the injection site by drainage through the lymphatics, with the rest of the dose remaining at the injection site depending on the design of the liposomes [1]. Yet, intralymphatic administration, has been shown to promote stronger immune responses [3]. Whilst this is not a realistic route for vaccination, it demonstrates the need to enhance the targeting of liposomal adjuvant to the lymphatics. Therefore, this project will develop thermostable targeted liposomal adjuvants which can be manufactured using flexible and adaptive processes and can be scaled up and down in a rapidly responsive mode.Measurable outcomes for this project are 1) Develop a novel lymphatic-targeting liposomal adjuvant that promotes robust immune responses and 2) Design and engineering of a microfluidics platform for bedside and continuous manufacturing of liposomal adjuvants.
背景疫苗是预防传染病的最有效和最具成本效益的方法。然而,全球获得疫苗的机会继续面临明显障碍:据估计,全世界仍有1 940万婴儿无法获得基本疫苗。为了解决这一问题,需要从生产商到接受者不间断地供应高质量疫苗。目前,这一供应链受到一系列因素的阻碍,包括疫苗供应不足,当地储存、处理和管理疫苗的能力有限,因为许多疫苗需要冷藏。因此,供应链的灵活性与有效和耐热疫苗系统的开发相结合是必要的。广泛的研究表明,脂质体作为疫苗抗原的合适佐剂。事实上,项目合作团队的工作已经证明,我们可以控制脂质体的理化属性(包括大小、电荷和双层刚性和组成),以增强佐剂功效[1]。因此,通过利用脂质体,我们能够减少生产有效疫苗所需的抗原量,从而提高疫苗产量。因此,我们可以使用这些纳米颗粒来提供疫苗生产的经济效率,并降低其生产成本和时间。除了它们的佐剂性质之外,申请人还证明了通过将抗原掺入这些双层纳米颗粒内,可以稳定蛋白质抗原。因此,脂质体有可能避免对疫苗冷链供应的需要,并提高当地的能力和供应。然而,脂质体疫苗是复杂的制剂,需要新的制造解决方案,以允许负担得起的和地理上的访问。为了解决这个问题,我们将在我们之前成功合作的基础上[2],使用新的微流体工艺来制造复杂的制剂,这将提高疫苗的有效性。因此,我们将在床边和通过可扩展的连续制造来满足他们的制造要求。为了促进疫苗配制中的剂量节省机会,该项目将开发靶向脊髓的疫苗。通常情况下,注射后,约50%的注射剂量脂质体通过引流从注射部位清除,其余剂量保留在注射部位,具体取决于脂质体的设计[1]。然而,淋巴内给药已被证明可促进更强的免疫应答[3]。虽然这不是一种现实的疫苗接种途径,但它表明需要增强脂质体佐剂对免疫系统的靶向。因此,本项目将开发热稳定的靶向脂质体佐剂,该佐剂可以使用灵活和自适应的工艺制造,并且可以以快速响应的模式按比例放大和缩小。本项目的可衡量成果是1)开发一种新型的靶向脂质体佐剂,促进强大的免疫应答和2)设计和工程化的微流体平台,用于床边和连续制造脂质体佐剂。
项目成果
期刊论文数量(0)
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其他文献
吉治仁志 他: "トランスジェニックマウスによるTIMP-1の線維化促進機序"最新医学. 55. 1781-1787 (2000)
Hitoshi Yoshiji 等:“转基因小鼠中 TIMP-1 的促纤维化机制”现代医学 55. 1781-1787 (2000)。
- DOI:
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LiDAR Implementations for Autonomous Vehicle Applications
- DOI:
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2021 - 期刊:
- 影响因子:0
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吉治仁志 他: "イラスト医学&サイエンスシリーズ血管の分子医学"羊土社(渋谷正史編). 125 (2000)
Hitoshi Yoshiji 等人:“血管医学与科学系列分子医学图解”Yodosha(涉谷正志编辑)125(2000)。
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Effect of manidipine hydrochloride,a calcium antagonist,on isoproterenol-induced left ventricular hypertrophy: "Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,K.,Teragaki,M.,Iwao,H.and Yoshikawa,J." Jpn Circ J. 62(1). 47-52 (1998)
钙拮抗剂盐酸马尼地平对异丙肾上腺素引起的左心室肥厚的影响:“Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,
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