Clinical development of DIOS-HFVac3: A pre-clinically effective multivalent vaccine for Lassa fever virus, Marburg virus, and Sudan ebolavirus

DIOSynVax是一家总部位于英国剑桥的临床阶段生物技术公司，该公司正在进行一项突破性项目，开发一种针对四种疾病的新型疫苗，这些疾病会对人类健康造成严重影响，包括埃博拉、拉萨、马尔堡和mpox。我们项目的主要目标是保护这些流行病风险和影响最高的中低收入国家(LMIC)的人口。Dios-HFVac3候选疫苗通过痘病毒疫苗载体提供RNA和密码子优化的序列，编码来自3种不同病毒的工程抗原-埃博拉和马尔堡病毒的糖蛋白和拉萨病毒的核蛋白，显示出对Mpox感染和/或疾病的保护。我们的候选疫苗在临床前试验中显示了良好的结果(图1，附录Q2)，显示出强大的免疫反应，保护相关动物模型免受埃博拉病毒-苏丹、马尔堡和拉萨病毒诱导的疾病的挑战该项目将承担五个不同的工作包，以确保临床疫苗制造过程以最高规格进行，以确保疫苗在GMP生产之前满足所有监管和安全标准，并为第一阶段临床研究和未来的生产规模做准备。这些措施包括CMC管理，包括种子材料和技术转让的资格、物理化学稳定性分析的工程批次运行、疫苗免疫原性的确认以及正式的毒理学研究，以及规划第一阶段临床研究并最终生成业务计划和技术案例。这些工作包中的每一个都旨在推动Dios-HFVac3疫苗进入临床试验和监管批准。这个项目不仅是为了创造一种疫苗，也是为了确保它能够在最需要的地方有效地生产和分发。我们正在致力于制造工艺，使我们能够大规模生产疫苗，包括未来在非洲的制造和随后的先进临床测试。该项目代表着在抗击流行病方面向前迈出的重要一步，利用尖端技术、多学科专业知识和疫苗开发方面成熟的记录，使我们的创新候选疫苗更接近临床开发、监管批准，并最终实施，以保护处于最大风险的人。

DIOSynVax, a clinical-stage biotechnology company based in Cambridge, UK, is working on a groundbreaking project to develop a novel vaccine against four diseases which cause outbreaks of high consequence to human health including Ebola, Lassa, Marburg and mpox . The primary goal of our project is to protect populations in low and middle-income countries (LMICs), where the risk and impact of these epidemic diseases are highest.The DIOS-HFVac3 candidate vaccine delivers RNA- and codon optimised sequences encoding engineered antigens derived from 3 different viruses - the glycoproteins of Ebola- and Marburg virus and the nucleoprotein of lassaviruses - via a poxviral vaccine vector, shown to protect from mpox infection and/or disease.Our vaccine candidate has demonstrated (Fig 1, Appendix Q2) promising results in preclinical trials, demonstrating a robust immune response protecting relevant animal models from challenge with Ebola-Sudan, Marburg, and Lassa virus induced disease, making it a promising candidate in the fight against these important epidemic disease threats.This project will undertake five distinct work packages important to ensure that the clinical vaccine manufacturing process is performed at the very highest specifications to ensure that the vaccine meets all the regulatory and safety criteria prior to GMP manufacturing and in preparation for Phase 1 Clinical studies and future manufacturing scaleup. These include CMC management comprising the qualification of the seed material and technology transfer, engineering batch run for physicochemical stability analysis, confirmation of vaccine immunogenicity as well as formal toxicology study, and planning of a Phase 1 clinical study and eventually the generation of a business plan and technical case. Each of these work packages is designed to advance the DIOS-HFVac3 vaccine towards clinical trials and regulatory approval.This project is not just about creating a vaccine, but also about ensuring it can be produced and distributed effectively where it is most needed. We are working on manufacturing processes that will allow us to produce the vaccine at scale, including future manufacturing and subsequent advanced clinical testing in Africa.This project represents a significant step forward in the fight against epidemic diseases, leveraging cutting-edge technology, multidisciplinary expertise, and a proven track record in vaccine development, bringing our innovative vaccine candidate closer to clinical development, regulatory approval, and ultimately, implementation to protect people at greatest risk.