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

DIOSynVax是一家位于英国剑桥的临床阶段生物技术公司，目前正在开展一项开创性的项目，开发一种新的疫苗，以对抗四种对人类健康造成严重后果的疾病，包括埃博拉、拉沙、马尔堡和天花。我们项目的主要目标是保护低收入和中等收入国家（LMICs）的人口，这些国家是这些流行病风险和影响最高的地方。DIOS-HFVac 3候选疫苗通过痘病毒疫苗载体递送编码来自3种不同病毒的工程抗原的RNA和密码子优化序列-埃博拉病毒和马尔堡病毒的糖蛋白以及拉沙病毒的核蛋白，我们的候选疫苗已经证明，（图1，附录Q2）在临床前试验中获得了有希望的结果，证明了稳健的免疫应答，可保护相关动物模型免受埃博拉-苏丹、马尔堡和拉沙病毒诱导的疾病的攻击，使其成为对抗这些重要流行病威胁的有希望的候选者。该项目将进行五个不同的工作包，以确保临床疫苗生产在GMP生产之前，以及在准备1期临床研究和未来生产规模扩大时，以最高质量标准执行工艺，以确保疫苗符合所有监管和安全性标准。其中包括CMC管理，包括种子材料和技术转让的确认、理化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毒理学研究，以及I期临床研究的规划，并最终生成商业计划和技术案例。这些工作包中的每一个都旨在推动DIOS-HFVac 3疫苗进入临床试验和监管批准。该项目不仅仅是创造一种疫苗，而且还确保它可以在最需要的地方有效地生产和分发。我们正在研究生产工艺，以便能够大规模生产疫苗，包括未来的生产和随后在非洲进行的高级临床试验。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、多学科专业知识以及在疫苗开发方面的良好记录，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中的人。

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.