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Yu, Wen-Han

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Yu

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Wen-Han

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Yu, Wen-Han
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    IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure
    (Springer Science and Business Media LLC, 2019-05-20) Lu, Lenette; Smith, Malisa; Yu, Krystle K. Q.; Luedemann, Corinne; Suscovich, Todd; Grace, Patricia; Cain, Adam; Yu, Wen-Han; McKitrick, Tanya; Lauffenburger, Douglas; Cummings, Richard; Mayanja-Kizza, Harriet; Hawn, Thomas R.; Boom, W. Henry; Stein, Catherine M.; Fortune, Sarah; Seshadri, Chetan; Alter, Galit
    Exposure to Mycobacterium tuberculosis (Mtb) results in heterogeneous clinical outcomes including primary progressive tuberculosis and latent Mtb infection (LTBI). Mtb infection is identified using the tuberculin skin test and interferon-γ (IFN-γ) release assay IGRA, and a positive result may prompt chemoprophylaxis to prevent progression to tuberculosis. In the present study, we report on a cohort of Ugandan individuals who were household contacts of patients with TB. These individuals were highly exposed to Mtb but tested negative by IFN-γ release assay and tuberculin skin test, ‘resisting’ development of classic LTBI. We show that ‘resisters’ possess IgM, class-switched IgG antibody responses and non-IFN-γ T cell responses to the Mtb-specific proteins ESAT6 and CFP10, immunologic evidence of exposure to Mtb. Compared to subjects with classic LTBI, ‘resisters’ display enhanced antibody avidity and distinct Mtb-specific IgG Fc profiles. These data reveal a distinctive adaptive immune profile among Mtb-exposed subjects, supporting an expanded definition of the host response to Mtb exposure, with implications for public health and the design of clinical trials.
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    Publication
    Exploiting glycan topography for computational design of Env glycoprotein antigenicity
    (Public Library of Science, 2018) Yu, Wen-Han; Zhao, Peng; Draghi, Monia; Arevalo, Claudia; Karsten, Christina; Suscovich, Todd J.; Gunn, Bronwyn; Streeck, Hendrik; Brass, Abraham L.; Tiemeyer, Michael; Seaman, Michael; Mascola, John R.; Wells, Lance; Lauffenburger, Douglas A.; Alter, Galit
    Mounting evidence suggests that glycans, rather than merely serving as a “shield”, contribute critically to antigenicity of the HIV envelope (Env) glycoprotein, representing critical antigenic determinants for many broadly neutralizing antibodies (bNAbs). While many studies have focused on defining the role of individual glycans or groups of proximal glycans in bNAb binding, little is known about the effects of changes in the overall glycan landscape in modulating antibody access and Env antigenicity. Here we developed a systems glycobiology approach to reverse engineer the complexity of HIV glycan heterogeneity to guide antigenicity-based de novo glycoprotein design. bNAb binding was assessed against a panel of 94 recombinant gp120 monomers exhibiting defined glycan site occupancies. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity as a proof-of concept. Our approach provides a new design strategy to predictively modulate antigenicity via the alteration of glycan topography, thereby focusing the humoral immune response on sites of viral vulnerability for HIV.