Plant-based production of a vaccine against gonorrhoea

基于植物的淋病疫苗生产

• 批准号: 2441454
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2441454
• 关键词: Plant; based; production; vaccine; against

The principal BBSRC priority area addressed by this project is 'Bioscience for renewable resources and clean growth - transforming industries through bio-based processes and products in a new low-carbon bioeconomy'. The project has a focus on plant biotechnology and therefore fits firmly within the BBSRC ambit. The proposal will introduce ways to improve the performance of vaccine production; in particular, transition to plant-based expression offers the potential for much reduced production energy costs, particularly in low income countries. Further, the targeting of antigen presenting cells is a disruptive technology, in the sense that it has the potential to overtake non-target vaccine approaches and thus address disease where induction of protective immunity is a major roadblock to vaccine development. The emergence of antimicrobial resistance (AMR) in Neisseria gonorrhoeae (Ng) has made combatting this bacterium an international priority. Ng is a leading cause of sexually transmitted infection (STI), responsible for >100 million cases annually. The inability to treat Ng adversely impacts female reproductive and foeto-maternal health (through pelvic inflammatory disease, ectopic pregnancy, infertility), while gonococcal infection is an important co-factor for HIV transmission. Furthermore, control of the gonococcal (Gc) transmission is threatened by the rise in antibiotic resistance. While vaccines are an important approach against the threat of resistant bacteria, Gc vaccine research has been hampered by the lack of protective immunity following infection, antigenic variation and previous failed attempts. However, recent advances have provided fresh impetus for vaccine development- an outer membrane vesicle vaccine (OMV) used against Neisseria meningitidis was associated with a modest yet significant protection against Ng, suggesting an approach to identify protective antigens. Vaccination strategies based on single recombinant Ng antigens have met with limited success, both in mouse infection models and clinical trials. A novel approach would be to use virus-like particles (VLPs)- or the more recently introduced large, synthetic macromolecular assemblies- as platforms for antigen delivery. These developments offer a hitherto untapped potential in vaccine design. In addition, the Derrick lab has recently developed a technology which allows the fusion of any number of antigens to a specific VLP or assembly. Critically, the method also allows for facile fusion of monoclonal antibodies: incorporation of antibodies directed against surface receptors thus allows targeting against specific subsets of dendritic or other antigen presenting cells. This development promises a game-changing approach to vaccine design, by combining target-driven antibody therapeutic technologies with traditional vaccine design. It could provide the breakthrough needed to circumvent the challenge of weak protective immunity against Ng reinfection. In addition, there is increasing interest in the use of plant-based expression systems for biopharmaceuticals and vaccines, particularly for application in developing countries. This project therefore aims to exploit methods developed by Anil Day for plastid-based expression, which enables very high yields of recombinant proteins, and apply them to modified VLPs, assemblies and Ng antigens.

该项目涉及的BBSRC主要优先领域是“可再生资源和清洁增长的生物科学-通过新的低碳生物经济中的生物工艺和产品改造工业”。该项目的重点是植物生物技术，因此完全符合BBSRC的范围。该提案将介绍改善疫苗生产绩效的方法;特别是，向植物表达的过渡有可能大大降低生产能源成本，特别是在低收入国家。此外，靶向抗原呈递细胞是一种破坏性技术，在这个意义上，它有可能超越非靶疫苗方法，从而解决其中诱导保护性免疫是疫苗开发的主要障碍的疾病。淋病奈瑟菌（Ng）中抗菌素耐药性（AMR）的出现使对抗这种细菌成为国际优先事项。Ng是性传播感染（STI）的主要原因，每年造成超过1亿例病例。无法治疗Ng对女性生殖和胎儿-孕产妇健康产生不利影响（通过盆腔炎、宫外孕、不孕症），而淋球菌感染是艾滋病毒传播的一个重要辅助因素。此外，淋球菌（Gc）传播的控制受到抗生素耐药性上升的威胁。虽然疫苗是对抗耐药细菌威胁的重要方法，但由于感染后缺乏保护性免疫力，抗原变异和先前失败的尝试，Gc疫苗研究受到阻碍。然而，最近的进展为疫苗开发提供了新的动力-用于脑膜炎奈瑟氏球菌的外膜囊泡疫苗（OMV）与对Ng的适度但显著的保护相关，这表明了一种鉴定保护性抗原的方法。基于单一重组Ng抗原的疫苗接种策略在小鼠感染模型和临床试验中都取得了有限的成功。一种新的方法是使用病毒样颗粒（VLP）-或最近引入的大型合成大分子组装体-作为抗原递送的平台。这些发展为疫苗设计提供了迄今尚未开发的潜力。此外，Derrick实验室最近开发了一种技术，可以将任何数量的抗原融合到特定的VLP或组件中。重要的是，该方法还允许单克隆抗体的容易融合：引入针对表面受体的抗体，从而允许靶向树突状细胞或其他抗原呈递细胞的特定亚群。这一发展通过将靶向驱动的抗体治疗技术与传统疫苗设计相结合，有望改变疫苗设计的游戏规则。它可以提供所需的突破，以规避针对Ng再感染的弱保护性免疫的挑战。此外，人们越来越关注将植物表达系统用于生物制药和疫苗，特别是用于发展中国家。因此，该项目旨在利用Anil Day开发的基于质体的表达方法，该方法能够获得非常高的重组蛋白产量，并将其应用于修饰的VLP，组装和Ng抗原。