PhD Thesis Defense: Matthew Stoner

"Sugar Coating Immunology: Dissecting Viral Antibody Responses Through the Lens of Glycomics"

Abstract

The human immune system is both complex and essential, providing protection against the innumerable pathogens that one encounters. As infectious disease continues to place a significant burden on the human population, a thorough understanding of this immune system is needed to better prevent and treat infectious disease. This work examines a small subset of this subject, specifically the role of glycosylations in viral antibody responses.  

We first describe the design and characterization of a hyperglycosylated hemagglutinin immunogen intended to improve the influenza vaccine antibody response. We describe the rational design process, screening those initial candidates via immunoassay, the characterization of a select candidate and its evaluation in a murine immunization experiment. We lastly discuss novel computational approaches for the design of such hyperglycosylated immunogens and showcase the capability relative to the rationally designed protein. 

Next, we introduce a novel methodology for the identification of Fc glycoforms and corresponding IgG subclass to allow for simpler examination of antibody glycan profiles. We show this method accurately identifies Fc glycopeptides both within recombinant monoclonal samples as well as polyclonal samples. Similarly, we show this method can simultaneously capture the glycoforms distributions within each subclass population. We also demonstrate that this approach can be modified to include antigen specific pulldown to gain even further insights into the antibody responses.

This work helps establish new methodologies for the study of glycobiology and immunology, while providing insights into several viral diseases.

Thesis Committee

• Jiwon Lee (chair)
• Margaret Ackerman
• Scott Gerber
• Goran Bajic (Icahn School of Medicine at Mount Sinai)

Contact

For more information, contact Thayer Registrar at thayer.registrar@dartmouth.edu .