CAREER: An ImmunoBioEngineering Platform for Rapid and Scalable Biomanufacturing of Universal Viral Vaccines

PI：Wen，Fei提案号：1653611流感流行每年导致25万-30万人死亡和300万-500万例重症病例。不幸的是，目前的流感疫苗提供有限的保护，需要季节性流感疫苗，并造成大流行的易感性，由于技术限制的鸡蛋为基础的制造。因此，开发用于通用流感疫苗的生物制造的快速且可扩展的系统具有巨大的社会影响。为了实现这一目标，该CAREER提案旨在开发一种基于酵母的系统，用于合成和工程化能够诱导针对流感病毒的普遍保护的人工流感样病毒（AILV）。它代表了一种新的方法，有可能从目前简单的天然病毒样颗粒合成方法转向复杂的设计师病毒样颗粒工程，用于开发下一代病毒疫苗。研究结果将用于加强本科生和研究生课程，这也将用于K-12外联工作，并提高公众在STEM领域的科学素养。基于酵母的AILV以前没有开发，由于几个分子和细胞的挑战。该提案将使用蛋白质工程、免疫学、合成生物学、生物化学和生物统计学的多学科方法来解决这些问题。具体来说，我们将研究：（1）酵母是否能够产生和组装关键的流感病毒蛋白到功能AILV;（2）如果得到的AILV可以引发保护性抗体和T细胞反应;（3）AILV的分子设计能够普遍保护。由此产生的基于酵母的AILV不仅将作为快速和可扩展的流感疫苗生物制造平台，而且还将用于探测免疫反应，以回答T细胞免疫学，蛋白质3D自组装等方面的核心问题。研究结果将用于加强本科生和研究生课程，这些课程也将用于K-12外展工作，并提高STEM领域的公众科学素养。 PI计划开发创造性的教学方法，使各级教育工作者能够适应，以改善学生的学习。

PI: Wen , FeiProposal No: 1653611Influenza epidemics result in 250,000-300,000 deaths and 3-5 million cases of severe illness annually. Unfortunately, current influenza vaccines offer limited protection requiring seasonal flu shots and pose pandemic susceptibility due to technological limitations of the egg-based manufacturing. Therefore, it is of great societal impact to develop a rapid and scalable system for biomanufacturing of universal flu vaccines. Towards this goal, this CAREER proposal aims to develop a yeast-based system for synthesizing and engineering artificial influenza-like viruses (AILVs) capable of inducing universal protection against influenza viruses. It represents a novel approach with the potential of shifting from current approach of simple natural virus-like particle synthesis to complex designer virus-like particle engineering for developing the next generation viral vaccines. Research findings will be used to strengthen the undergraduate and graduate curricula, which will also be used in K-12 outreach endeavors and increase public scientific literacy in the STEM fields.Yeast-based AILVs have not been previously developed due to several molecular and cellular challenges. This proposal will address these issues using a multi-disciplinary approach interfacing protein engineering, immunology, synthetic biology, biochemistry, and biostatistics. Specifically, we will investigate: (1) if yeast is capable of producing and assembling key influenza viral proteins into functional AILVs; (2) if the resulting AILVs can elicit protective antibody and T-cell responses; and (3) the molecular design of AILVs capable of universal protection. The resulting yeast-based AILVs will not only serve as a rapid and scalable influenza vaccine biomanufacturing platform, but also will be used to probe immune responses to answer central questions in T-cell immunology, 3D self-assembly of proteins, and more. Research findings will be used to strengthen the undergraduate and graduate curricula, which will also be used in K-12 outreach endeavors and increase public scientific literacy in the STEM fields. PI plans to develop creative pedagogies that are adaptable by educators at all levels for improved student learning.