Deep Mutational Scanning to Discover Viral Escape from Polyclonal Antibodies Targeting SARS-CoV-2

Presenter's Name(s)

Benjamin WillFollow

Abstract

The SARS-CoV-2 pandemic tested the limits of vaccine technology and the predictions of serological tools. The dynamic interplay between an evolving virus and drifting antibody responses at the population level propagated development of new strategies to quantify vaccine epitopes and viral escape. We employ yeast surface display of a mutagenic SARS-CoV-2 Spike protein library and next generation sequencing to map epitopes and escape mutations of polyclonal antibody repertoires. We developed a method to crosslink and capture antibodies, permitting assessment at a larger dynamic range of affinity. This strategy provides greater insight into the “tug-of-war” between viral escape and antibody generation.

Primary Faculty Mentor Name

Dev Majumdar

Graduate Student Mentors

Zachary Miller

Faculty/Staff Collaborators

Jessica Crothers

Student Collaborators

Lily Kjendal, Emily Clark

Status

Undergraduate

Student College

College of Arts and Sciences

Second Student College

Honors College

Program/Major

Biochemistry

Primary Research Category

Biological Sciences

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Deep Mutational Scanning to Discover Viral Escape from Polyclonal Antibodies Targeting SARS-CoV-2

The SARS-CoV-2 pandemic tested the limits of vaccine technology and the predictions of serological tools. The dynamic interplay between an evolving virus and drifting antibody responses at the population level propagated development of new strategies to quantify vaccine epitopes and viral escape. We employ yeast surface display of a mutagenic SARS-CoV-2 Spike protein library and next generation sequencing to map epitopes and escape mutations of polyclonal antibody repertoires. We developed a method to crosslink and capture antibodies, permitting assessment at a larger dynamic range of affinity. This strategy provides greater insight into the “tug-of-war” between viral escape and antibody generation.