Date of Award
2024
Document Type
Thesis (Ph.D.)
Department or Program
Engineering Sciences
First Advisor
Jiwon Lee
Abstract
Adaptive immunity, comprised in part by the antibody repertoire, is the cornerstone of our ability to remain healthy amongst the plethora of pathogenic challenges we encounter daily. Despite the importance of understanding antibody repertoire development, much remains unknown about the composition and evolution of circulating antibodies in response to viral challenges. To better understand antibody repertoire development, we profiled the serum antibody repertoire using a combination of next-generation sequencing and serum antibody proteomics in the predominantly naïve response against SARS-CoV-2 spike and the recalled response to influenza hemagglutinin. The response to SARS-CoV-2 spike in four convalescent individuals was diverse (consisting of between 59 and 167 clonotypes) and predominately targeted regions of the protein which were inaccessible on prefusion spike and likely non-protective. Only a small fraction of these antibodies could target any tested SARS-CoV-2 variants. Few of the recombinantly expressed antibodies neutralized the virus, and those that did neutralize were orders of magnitude weaker than a representative therapeutic antibody; however, all antibodies showed ADCP, ADCC, and ADCD activity. In one donor, an antibody with high binding to another human coronavirus, HKU1, dominated the serum repertoire and had levels of somatic hypermutation commonly observed in recalled antibodies. This antibody was the only among a panel we characterized which maintained binding to the highly mutated B.1.1.529 variant.
Recommended Citation
Curtis, Nicholas C., "CHARACTERIZATION OF ANTIBODY REPERTOIRES DEVELOPED FROM NAIVE AND RECALL RESPONSES" (2024). Dartmouth College Ph.D Dissertations. 315.
https://digitalcommons.dartmouth.edu/dissertations/315
