Developing novel vaccine formulations for single-dose immunisation

开发单剂量免疫的新型疫苗配方

• 批准号: 2126185
• 金额: --
• 依托单位: University of Oxford
• 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: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2126185
• 关键词: Developing; novel; vaccine; formulations; single

Almost all current vaccines require administration in two or three doses and at specific time intervals to achieve full efficacy. Single dose immunisation is a long-standing concept that could significantly improve vaccination coverage globally. Attempts to develop a single dose vaccine have so far been unsuccessful with one of the key obstacles being the design of formulations capable of achieving pulsatile (time-determined) vaccine release in vivo, while preserving antigen stability and immunogenicity. This project aims to develop vaccine delivery formulations that would allow prime-boost vaccination to be combined into a single dose by encapsulating the booster vaccine into microparticles and administering it together with the priming vaccine in soluble form. The timing and kinetics of the booster vaccine release will be determined by the chemical composition and method of preparation. A particular focus will be placed on utilising novel production techniques to develop delivery formulations (particles or gels) to stabilise the vaccine antigen in vivo. Various biocompatible polymers with a range of degradation profiles will be used to produce particles with different kinetics (continuous/pulsatile) and time to antigen release. Following in vitro analysis of particle size, monodispersity, encapsulation efficiency and release kinetics under simulated "in vivo" conditions, new formulations will be tested in vivo for pharmacokinetics, safety and immunogenicity. Development of novel formulation and particle production will encompass process validation and explore scale-up and suitability for GMP production. Initially the formulations will be optimised using a model antigen and will then move to testing the process using two of the currently most promising vaccine platforms, virus like particles (VLPs) and viral vectors. Successful formulations will be taken forward into mouse disease challenge models and compared with standard prime-boost regimens. This project has emphasis on chemical composition and formulation and the ideal candidate will have background in chemistry or pharmacology.

目前几乎所有的疫苗都需要分两次或三次接种，并在特定的时间间隔内接种，以达到完全的疗效。单剂免疫是一个长期存在的概念，可以显著提高全球疫苗接种覆盖率。迄今为止，开发单剂量疫苗的尝试尚未成功，其中一个关键障碍是能够实现体内脉冲（时间确定的）疫苗释放同时保持抗原稳定性和免疫原性的制剂的设计。该项目旨在开发疫苗递送制剂，通过将加强疫苗封装在微粒中并将其与可溶形式的初免疫苗一起施用，将初免-加强疫苗接种组合成单剂量。加强疫苗释放的时间和动力学将由化学组成和制备方法决定。将特别关注利用新型生产技术开发递送制剂（颗粒或凝胶）以稳定体内疫苗抗原。具有一系列降解特征的各种生物相容性聚合物将用于生产具有不同动力学（连续/脉冲）和抗原释放时间的颗粒。在模拟“体内”条件下对粒度、单分散性、包封效率和释放动力学进行体外分析后，将在体内测试新制剂的药代动力学、安全性和免疫原性。新配方和颗粒生产的开发将包括工艺验证，并探索规模扩大和GMP生产的适用性。最初，将使用模型抗原优化制剂，然后使用目前最有前途的两种疫苗平台，病毒样颗粒（VLP）和病毒载体来测试该过程。成功的制剂将被用于小鼠疾病挑战模型，并与标准的初免-加强方案进行比较。该项目强调化学成分和配方，理想的候选人将具有化学或药理学背景。