Structure-guided vaccine, antibody and drug discovery

Abstract

Thesis (Ph.D.)--University of Washington, 2022The current pandemic, COVID19, will remain engraved in our history. However, if not the rapid response for vaccine and antibody development has been made from the outset, this wound might be even deeper and more anguished. Advances in mRNA vaccine delivery and pre-fusion spike stabilization were the cornerstones of this success. And this footstone cannot be made without the structure information we gathered in the past several years. Here, I will show how important and necessary the structure information is for facilitating and even initiating vaccine, antibody and drug development. To illustrate this argument, I am going to cover several examples across coronavirus, henipavirus and orthopoxvirus structure studies using CryoEM and CryoET techniques complemented with biochemical and biophysical assays, such as ELISA, BLI and pseudovirus neutralization. The results from these studies are great examples of how structure information can reshape our understanding of diverse biological systems. And for the virology field, these new understandings are so valuable for potential pandemic preparation. If the disaster reemerges, we will never be more prepared by that time

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