I-Corps: A Multi-Antigen Vaccine Delivery System for the Effective Induction of Mucosal Immunity

这个I-Corps项目更广泛的影响/商业潜力是开发一个新的疫苗发现平台。2019冠状病毒病大流行让我们看到迫切需要能够有效提供对抗粘膜感染的疫苗的技术。粘液感染，如流感和轮状病毒，占美国每年记录的传染病病例的70%以上，占全球所有感染的50%以上。这种高感染率是因为大多数病原体要么直接感染粘膜组织，要么开始它们在整个身体的粘膜部位侵入（即，鼻子、肠子和嘴巴）。 该技术解决了将疫苗有效递送到粘膜组织的需求，提供了强大的免疫反应，并且可以快速开发和扩大规模以应对新出现的大流行病，从而可能挽救数十万人的生命。除了快速反应之外，所提出的疫苗递送系统可以一次与多种抗原一起使用，从而潜在地减少患者一生中所需的疫苗接种次数。拟议的疫苗平台是无针的，使其能够在诊所外管理，减少对高技能人员的需求和管理成本，特别是在低收入国家。这个I-Corps项目是基于开发外细胞膜囊泡作为疫苗输送平台。外膜囊泡（OMV）是由具有调节免疫系统的能力的细菌天然产生的球形脂质双层。以前，OMV被工程化以在其外表面上展示抗原，从而充当自佐剂疫苗平台，其在动物模型中显示出作为可注射疫苗的前景。已经在小鼠模型中研究了OMV平台的进一步修饰以实现多种不同抗原的共递送的免疫潜力。初步工作表明，这一特征对疫苗工程产生潜在的好处。此外，通过对猪进行口腔接种，OMV被证明可以诱导强大的粘膜免疫力，而无需注射。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the development of a novel vaccine discovery platform. The COVID-19 pandemic has opened our eyes to the urgent need for technologies capable of effectively delivering vaccines that combat mucosal infections. Mucosal infections, such as influenza and rotavirus, make up more than 70% of the yearly cases of infectious diseases recorded in the US, and more than 50% of all infections worldwide. This high infection rate is because most pathogens either infect mucosal tissues directly or begin their invasion at mucosal sites throughout the body (i.e., the nose, intestines, and mouth). The proposed technology solves the need to effectively deliver vaccines to mucosal tissue, providing a robust immune response, and can be rapidly developed and scaled up to respond to emerging pandemics, saving potentially hundreds of thousands of lives. In addition to being rapid response, the proposed vaccine delivery system can be used with multiple antigens at once, potentially reducing the number of vaccinations required throughout a patient’s lifetime. The proposed vaccine platform is needle-free, allowing it to be administered outside of clinics, reducing the need for highly skilled personnel and administration costs especially in low-income countries.This I-Corps project is based on the development of outer cell membrane vesicles as a vaccine delivery platform. Outer membrane vesicles (OMVs) are spherical lipid bilayers naturally produced by bacteria that possess the ability to modulate the immune system. Previously, OMVs were engineered to display antigens on their exterior surface, thereby acting as a self-adjuvanted vaccine platform that has shown promise in animal models as an injectable vaccine. Further modification of the OMV platform to enable the co-delivery of multiple different antigens has been investigated for its immunological potential in a mouse model. Preliminary work has shown this feature to yield potential benefits for vaccine engineering. Additionally, through buccal vaccination in swine, OMVs were shown to induce robust mucosal immunity, without the need for injection.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.