MEMP PhD Thesis Defense: Amanda Hornick

Multiplexed, High-Throughput Serum Assays Using Lentivirus Display to Analyze Antibody Responses

Antibodies are an integral part of our immune system. Whether generated through antigen exposure or provided as therapeutics, antibodies can direct targeted responses against specific antigens on foreign substances, pathogens, and cells. Therefore, accurately, efficiently, and comprehensively characterizing the antigen recognition capabilities of individuals’ antibody repertoires is critical to understanding individuals’ extent of protection against disease. As existing antibody measurement techniques are limited in their ability to test antibodies’ recognition of multiple, native-conformation antigens in a single reaction, we developed assays that employ libraries of hybrid pseudo-typed, DNA-barcoded lentiviruses to measure antibodies in a multiplexed, high-throughput manner. To record interactions between library lentiviruses and serum antibodies, our assays utilize cells expressing either an Fc receptor or viral entry receptor to measure antibodies’ binding or neutralization of their target antigens, respectively. During the COVID-19 pandemic, we constructed a lentivirus library with members displaying SARS-CoV-2 spike protein variants and other viral surface proteins to study the effects of infection, vaccination, and monoclonal antibody therapies on antiviral antibody responses. Using sera from pre-pandemic, COVID-19 convalescent, and COVID-19 vaccinated donors and validating our assays’ readouts against those from established immunoassays, we were able to demonstrate the ability of our assays to differentiate between samples with and without antibodies against antigens of interest. By engineering our lentiviruses to display additional antigens and cell lines to express other Fc and viral entry receptors, we can further enhance our ability to characterize how different diseases, and medical interventions impact the development and maintenance of targeted antibody responses. 

Thesis Supervisor:
Michael Birnbaum, Ph.D. 
Associate Professor of Biological Engineering, MIT 

Thesis Committee Chair:
Douglas Lauffenburger, Ph.D.
Ford Professor of Engineering, MIT

Thesis Readers:
Facundo Batista, Ph.D.
Phillip T. and Susan M. Ragon Professor of Biology, MIT 
Associate Director and Scientific Director of the Ragon Institute of MGH, MIT, and Harvard 

Duane Wesemann, M.D., Ph.D.
Associate Professor of Medicine, Harvard Medical School 
Associate Physician, Brigham and Women’s Hospital

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Topic: Amanda Hornick MEMP PhD Thesis Defense
Time: Monday, September 29, 2025, 9:30 AM Eastern Time (US and Canada)

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