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

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

PI: Wen , Fei Proposal No: 1653611 Influenza 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.