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

克里米亚-刚果出血热(CCHF)通过受感染的扁虱和携带病毒的动物宿主传播给人类。CCHF还通过密切接触和体液传播给人类，致死率为10%-40%。CCHF主要限于较温暖的国家，因此任何疫苗都需要经受住极端温度。CCHF病毒已在非洲、亚洲、中东、东欧和西南欧的扁虱中发现，这些地区是扁虱病毒中最广泛的地理区域，对人类健康构成潜在威胁。随着全球持续变暖，扁虱的迁徙加上大型动物的传播，将CCHF置于疫苗开发的高度优先地位。随着症状的迅速出现，从典型的病毒感染发展到从几个管路出血到无法控制的出血，需要一种不仅能预防CCHF而且能治疗CCHF的疫苗。PHION Treateutics已经开发出一种名为Rala的肽，它可以将信使RNA(MRNA)传递到抗原产生细胞，以产生预防性T细胞记忆和治疗性CD8+疫苗反应。该项目的愿景是应用PHION的技术开发一种疫苗，使用Rala来传递编码3个CCHF抗原的mRNA，不仅将防止患者感染CCHF，还将治疗那些感染CCHF的患者。PHION是唯一一家拥有这种Rala多肽的公司，这种多肽可以将多个mRNA抗原序列浓缩成纳米颗粒，然后冷冻干燥成一种在室温下稳定18个月的产品。由于我们的信使核糖核酸疫苗不需要冷链储存，因此可以广泛分发。临床前目标是在12个月内设计，以在挑战模型中制定和评估CCHF疫苗，以便知道最佳剂量和注射方案。这使PHION准备好进行毒理学、IND备案，并以最佳产品进入临床。我们的Rala/mRNA疫苗还具有制造和可伸缩性的优势，其中包括一个全自动化的成本效益高的过程，只需要在生产后进行无菌过滤。这一平台技术在该项目中的发展可能成为新一代室温mRNA疫苗的催化剂。此外，这项投资进一步验证了PHion的平台技术，进一步加强了英国在疫苗市场的地位，具有潜在的全球影响。

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.