A Peptide-mRNA Vaccine for Crimean-Congo Haemorrhagic Fever (CCHF)

克里米亚-刚果出血热（CCHF）通过受感染的蜱虫和携带病毒的动物宿主传播给人类。CCHF也通过密切接触和体液传播给人类，死亡率为10- 40%。CCHF仅限于主要温暖的国家，因此任何疫苗都需要承受极端温度。CCHF病毒已在非洲、亚洲、中东、东欧和西南欧的蜱虫中发现，这是任何蜱虫病毒的最广泛地理区域，对人类健康构成潜在威胁。随着全球持续变暖，蜱虫的迁移加上大型动物传播，使CCHF成为疫苗开发的优先事项。随着症状迅速发作，从典型的病毒感染发展为多个管道出血，再到不受控制的出血，需要一种不仅能预防CCHF而且能治疗CCHF患者的疫苗。pHion Therapeutics已经开发了一种称为RALA的肽，其可以将信使RNA（mRNA）递送至抗原产生细胞以产生预防性T细胞记忆和治疗性CD 8+疫苗应答。该项目的愿景是应用pHion的技术开发一种疫苗，使用RALA递送编码3种CCHF抗原的mRNA，不仅可以预防患者感染CCHF，还可以治疗感染CCHF的患者。pHion是唯一一家拥有这种RALA肽的公司，这种肽可以将多个mRNA抗原序列浓缩成纳米颗粒，这些纳米颗粒被冻干成在室温下稳定18个月的产品。由于我们的mRNA疫苗不需要冷链储存，这使得广泛分布成为可能。临床前目标设计为在12个月内配制和评估攻毒模型中的CCHF疫苗，以便了解最佳剂量和注射方案。这使pHion准备好进行毒理学，IND申请并进入临床最佳产品。我们的RALA/mRNA疫苗还具有制造和可扩展性优势，包括仅需要无菌过滤后生产的全自动化成本效益工艺。该项目中该平台技术的发展可能是新一代室温mRNA疫苗的催化剂。此外，这项投资代表了对pHion平台技术的进一步验证，进一步巩固了英国在疫苗市场的地位，具有潜在的全球影响力。

The Crimean-Congo Haemorrhagic Fever (CCHF) is transmitted to humans via infected ticks and through animal reservoirs that carry the virus. CCHF is also transmitted to humans through close contact and bodily fluids and has a fatality rate of 10-40%. CCHF is restricted to primarily warmer countries so any vaccine needs to withstand extreme temperatures. The CCHF virus has been found in ticks in Africa, Asia, the Middle East, Eastern Europe and South Western Europe, the widest geographic region of any tick virus which is a potential threat to human health. With continued global warming, the migration of ticks coupled with large animal transmission, places CCHF on the high priority for vaccine development. With a rapid onset of symptoms which progress from typical viral infections into haemorrhaging from several tracts to uncontrolled bleeding, there is a need for a vaccine that not only prevents CCHF but also treats those with CCHF. pHion Therapeutics have developed a peptide termed RALA that can deliver messenger RNA (mRNA) to antigen producing cells to produce a prophylactic T-Cell memory and a therapeutic CD8+ vaccine response. The vision for this project is to apply pHion's technology to develop a vaccine using RALA to deliver mRNA encoding 3 CCHF antigens that will not only prevent patients contracting CCHF but will also treat those that are infected with CCHF. pHion is the only company that has this RALA peptide which can condense multiple mRNA antigenic sequences into nanoparticles which are lyophilised into a product that is stable for \>18 months at room temperature. As our mRNA vaccines do not require cold-chain storage, this enables wide-spread distribution. The pre-clinical objectives are designed over 12 months to formulate and assess the CCHF vaccine in challenge models so that the optimal dose and injection regimen is known. This places pHion ready to progress to toxicology, IND filing and into the clinic with the optimal product. There are also manufacturing and scalability advantages of our RALA/mRNA vaccines which include a fully automated cost -effective process that only requires sterile filtration post-production. The development of this platform technology in this project could be the catalyst for a new generation of room-temperature mRNA vaccines. In addition, this investment represents a further validation of pHion's platform technology, further strengthening the UK's position in the vaccine market with potential for global impact.