High-throughput analysis of native antibody repertoires for therapeutics discovery




Wang, Bo, Ph. D. in chemical engineering

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Adaptive immunity is the foundation of recognition and protection against a diverse array of pathogens. The humoral arm of adaptive immunity whose most significant effector mechanism relies on antibodies is critical for protection against many viral and bacterial pathogens. Additionally, antibodies are extremely important for clinical medicine either as therapeutics or for detection purposes. As a result, there is great interest in the development of technologies for isolating therapeutically or diagnostically useful antibodies from immunized animals or from patients. In this work I describe several high throughput approaches for the “mining” of the mammalian adaptive antibody response for the purpose of isolating antibodies with high affinity and selectivity towards desired antigens. The first technology capitalizes on the fact that the antibody repertoire encoded by B cells in the draining lymph node from the immunization site is highly enriched for antibodies specific to the immunogen. The second technology takes advantage of repertoire analysis by next-generation sequencing and yeast display for antibody discovery. The third technology integrates high-throughput V [subscript H] :V [subscript L] pairing with yeast surface display to enable rapid, high-throughput screening of all native antibodies in the repertoire. These three technologies have been used to identify a large panel of antibodies against several different pathogens, including Ebola virus, ricin, influenza virus, and HIV-1 virus. These technologies will continue to play a critical role in adaptive immunity exploration for new therapeutics discovery, and in characterization of immune responses elicited by vaccination or natural infection to guide design of more effective vaccines.


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