#1: Computational ImmunoEngineering & the Synthetic Biology Revolution: lessons in T-cell receptor engineering, antibody engineering, (....) - #2: Applied computational immunology: validation of a universal vaccine techn. in influenza & pigs
Abstract #1: Jacob Glanville
Adaptive immunity is predicated on combinatorial complexity. This complexity enables the body to continuously defend itself against a universe of ever-evolving pathogens, but has also frustrated efforts to analyze and characterize adaptive immune function. In the last decade, advances in high-throughput sequencing and high-throughput synthesis have dramatically altered our ability to interrogate and alter adaptive immune repertoires at scale. Here we present a history of the emerging field of computational immunology and immunoEngineering through a series of case studies in B-cell and T-cell repertoire sequencing, single-cell sequencing technologies, antibody repertoire engineering, T-cell specificity engineering, and recent advances in computational methods for rapidly identifying the specificity of TCRs and BCRs from primary sequence using the GLIPH algorithm.
Abstract #2: Sarah Ives
In the last century, vaccines have significantly reduced and even eradicated many historically pervasive pathogens. However, rapidly mutating or naturally polymorphic pathogens of HIV, influenza, Chagas disease, sleeping sickness, Dengue and Zika continue to pose challenges to vaccine science. Here, we demonstrate a universal influenza vaccine Centivax using a computationally guided epitope focusing technology. In two repeat studies in sus scrofa (pig), the epitope focusing vaccine induced antibodies against 39 viral strains of influenza spanning the last century, including all pandemic events (1918 H1N1 Spanish flu, 1957 H2N2 Asian flu, 1968 H3N2 Hong Kong flu, 1977 H1N1 Russian flu, 2002 H3N2 Fujian flu, and 2009 H1N1 Swine flu). In a pre-2009 Centivax design, the vaccine further elicited broad neutralizing immunity against future viral strains. Observation of an inverse-dose response, single antigen tests, and 159 monoclonal pig antibodies recovered from immunized animals further clarify the mechanism of epitope focusing by Centivax. We explore immunological features of this broad response and discuss plans to apply the technology to other rapidly mutating pathogen systems.
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