Heat proofing Immunity: Pioneering a Thermally Resilient Ensilicated mRNA-LNP Vaccine Platform

EnsiliTech与Afrigen和Emervax合作，打算开发一种抗汉滩病毒（HTNV）的脂质纳米颗粒（mRNA-LNP）热稳定的青贮信使核糖核酸疫苗，这种疫苗可以在全球迅速和公平地部署。汉坦病毒家族的汉坦病毒主要存在于亚洲，尽管它在全球范围内都有发生。它通过啮齿动物（在本例中为田鼠）作为人类的携带者传播，并引起肾综合征出血热（HFRS），导致高达15%的感染者死亡，全球每年估计有20万例病例。目前还没有市售疫苗。我们认为，我们的共同努力和资源能够有助于研制一种安全、有效和现代的疫苗来对付这种病毒。我们强烈设想一个公平获得能够预防被忽视的传染病的最新疫苗的世界。Emervax将提供他们在研究其他汉坦病毒（如安第斯病毒）方面的知识和经验，以开发编码所需抗原的mRNA盒。Afrigen将生产原料药（即原料药）和包括在LNP内封装的药品。EnsiliTech将利用青贮技术研究mRNA和mRNA- lnp的稳定性，使其成为室温稳定的疫苗。这使得冷链物流过时，并通过延长保质期和增强热稳定性来增加可及性和可用性。我们相信这直接符合拨款竞争的范围和目标。我们期望这个项目的结果为我们提供：*通过体外和体内免疫原性证明了一种新的抗HTNV的抗原mRNA结构，这得到了随后的第一代mRNA- lnps的挑战研究的支持；*建立mRNA-LNP孵化术及其稳健方案；*通过青贮制备耐热疫苗；*在啮齿类动物体内肌肉注射的保护性免疫效果。该项目的影响将是使这一工作流程能够以其他被忽视的疾病为模板，并为诸如x病等新出现的传染性病原体提供一个平台。该项目还涉及最终疫苗配方走向市场的所有关键方面。所创造的知识产权（IP）将使政府机构或非政府组织获得许可证，并支持生产和分销。总的来说，我们的共同努力将介入并为该联盟提供进一步的机会，使其成为改善全球健康的重要贡献者。

EnsiliTech working with Afrigen and Emervax intend to develop a thermostable ensilicated messenger ribonucleic acid in lipid nanoparticle (mRNA-LNP) vaccine against the Hantaan virus (HTNV) that can be rapidly and equitably deployed globally.The Hantaan virus of the hantavirus family is predominantly present in Asia, although it occurs around the globe. It is transmitted through rodents, in this case the field mouse, as carriers to humans and causes haemorrhagic fever with renal syndrome (HFRS) that results in mortality up to 15% of infected individuals with yearly estimates of 200,000 cases globally. There is no vaccine commercially available.We believe that our combined effort and resources can contribute to the development of a safe, effective and modern vaccine against this virus. We strongly envision a world with equitable access to the latest vaccines that can prevent neglected infectious diseases. Emervax will provide their knowledge and experience in working on other Hantaviruses such as the Andes virus to the development of an mRNA cassette encoding the desired antigen. Afrigen will manufacture the drug substance (i.e. active pharmaceutical ingredient, API) and drug product which includes encapsulation within the LNP. EnsiliTech will investigate stabilisation of mRNA and mRNA-LNP using the ensilication technology, making it a room-temperature stable vaccine. This renders the cold chain logistics obsolete and increases accessibility and availability by extending shelf life and enhanced thermal stability. We believe this directly aligns with the scope and aims of the grant competition.We anticipated the results of this project to provide us with:* A novel antigenic mRNA construct efficacious against the HTNV demonstrated through _in vitro_ and _in vivo_ immunogenicity supported by challenge studies with subsequent first generation of mRNA-LNPs;* The establishment of mRNA-LNP ensilication and robust protocol thereof;* Thermostable vaccine formulation through ensilication;* Protective immunisation efficacy through intramuscular delivery _in vivo_ in rodents.The impact of the project would be the ability of this workflow to be templated on other neglected diseases and provide a platform for those emerging infectious pathogens such as Disease X. This project also addresses all key aspects towards the route to market for the final vaccine formulations. The created intellectual property (IP) will enable governmental bodies or non-governmental organisations to take a licence and support the manufacturing and distribution. Overall, our combined effort would intercalate and provide further opportunity for this consortium to become important contributors in the effort to improve global health.