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

EnsiliTech与Afrigen和Emervax合作，旨在开发一种针对汉坦病毒（HTNV）的热稳定的硅化信使核糖核酸脂质纳米颗粒（mRNA-LNP）疫苗，该疫苗可以在全球范围内快速公平地部署。汉坦病毒家族的汉坦病毒主要存在于亚洲，尽管它在地球仪各地都有发生。它通过啮齿动物传播，在这种情况下是田鼠，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200，000例。我们相信，通过我们的共同努力和资源，可以有助于研制出一种针对这种病毒的安全、有效和现代化的疫苗。我们强烈设想一个能够公平获得最新疫苗的世界，以预防被忽视的传染病。Emervax将提供他们在其他汉坦病毒（如安第斯山脉病毒）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（即活性药物成分，API）和制剂（包括LNP内的封装）。EnsiliTech将研究使用硅化技术稳定mRNA和mRNA-LNP，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提高可达性和可用性。我们认为这与资助竞争的范围和目标直接一致。我们预计该项目的结果将为我们提供：* 一种新的抗原性mRNA构建体，其通过体外和体内免疫原性证明对HTNV有效，并得到随后第一代mRNA-LNP的挑战研究的支持;* mRNA-LNP硅化及其稳健方案的建立;* 通过硅化的热稳定疫苗制剂;* 在啮齿动物体内通过肌肉注射的保护性免疫效力。该项目的影响将是该工作流程能够在其他被忽视的疾病上模板化，并为那些新兴的传染性病原体（如X疾病）提供平台。该项目还涉及最终疫苗制剂上市途径的所有关键方面。创建的知识产权（IP）将使政府机构或非政府组织能够获得许可证，并支持制造和分销。总的来说，我们的共同努力将使这个联合体成为改善全球健康努力的重要贡献者，并为之提供进一步的机会。

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.