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)的耐热硅化脂纳米信使核糖核酸(mRNA-LNP)疫苗，该疫苗可以在全球快速而公平地部署。汉滩病毒家族的汉滩病毒主要存在于亚洲，尽管它在全球都有发生。它通过啮齿动物传播，在这种情况下是野鼠，作为人类的携带者，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。我们相信，我们的共同努力和资源可以帮助开发出一种安全、有效和现代的疫苗来对抗这种病毒。我们强烈设想一个能够公平获得最新疫苗的世界，这些疫苗可以预防被忽视的传染病。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信使核糖核酸盒。Afrigen将生产药物物质(即活性药物成分，API)和药物产品，其中包括在LNP中的封装。EnsiliTech将使用使其稳定的技术研究mRNA和mRNA-LNP的稳定性，使其成为一种室温稳定的疫苗。这使得冷链物流过时，并通过延长货架寿命和增强热稳定性来增加可及性和可用性。我们相信这与赠款竞争的范围和目标直接一致。我们预计这一项目的结果将为我们提供：*一种新的抗原性mRNA结构，通过体外和体内试验证明对HTNV具有有效的免疫原性，并得到后续第一代mRNA-LNPs的挑战研究支持；*建立mRNA-LNP的赋值及其可靠的方案；*通过赋值的方法制备耐热疫苗；*通过活体内肌肉注射的保护性免疫效力。该项目的影响将是这一工作流程能够以其他被忽视的疾病为模板，并为那些新出现的传染病病原体提供一个平台。该项目还解决了最终疫苗配方推向市场的所有关键方面。创造的知识产权(IP)将使政府机构或非政府组织能够获得许可，并支持制造和分销。总体而言，我们的共同努力将插入并为该联盟提供进一步的机会，使其成为改善全球卫生努力的重要贡献者。

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.