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Lingwood, Daniel

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Lingwood

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Daniel

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Lingwood, Daniel
Author's Publications: search.filters.isAuthorOfPublication.489287c3-2b5f-42be-9001-871a900d15a4

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    Novel in vitro booster vaccination to rapidly generate antigen-specific human monoclonal antibodies
    (The Rockefeller University Press, 2017) Sanjuan Nandin, Irene; Fong, Carol; Deantonio, Cecilia; Torreno-Pina, Juan A.; Pecetta, Simone; Maldonado, Paula; Gasparrini, Francesca; Ordovas-Montanes, Jose; Kazer, Samuel W.; Kjaer, Svend; Borley, Daryl W.; Nair, Usha; Coleman, Julia A.; Lingwood, Daniel; Shalek, Alex K.; Meffre, Eric; Poignard, Pascal; Burton, Dennis R.; Batista, Facundo
    Vaccines remain the most effective tool to prevent infectious diseases. Here, we introduce an in vitro booster vaccination approach that relies on antigen-dependent activation of human memory B cells in culture. This stimulation induces antigen-specific B cell proliferation, differentiation of B cells into plasma cells, and robust antibody secretion after a few days of culture. We validated this strategy using cells from healthy donors to retrieve human antibodies against tetanus toxoid and influenza hemagglutinin (HA) from H1N1 and newly emergent subtypes such as H5N1 and H7N9. Anti-HA antibodies were cross-reactive against multiple subtypes, and some showed neutralizing activity. Although these antibodies may have arisen as a result of previous influenza infection, we also obtained gp120-reactive antibodies from non–HIV-infected donors, indicating that we can generate antibodies without prior antigenic exposure. Overall, our novel approach can be used to rapidly produce therapeutic antibodies and has the potential to assess the immunogenicity of candidate antigens, which could be exploited in future vaccine development.
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    Reconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation
    (Nature Publishing Group, 2016) Villar, Rina F.; Patel, Jinal; Weaver, Grant C.; Kanekiyo, Masaru; Wheatley, Adam K.; Yassine, Hadi M.; Costello, Catherine E.; Chandler, Kevin B.; McTamney, Patrick. M.; Nabel, Gary J.; McDermott, Adrian B.; Mascola, John R.; Carr, Steven A.; Lingwood, Daniel
    Activation of immune cells (but not B cells) with lectins is widely known. We used the structurally defined interaction between influenza hemagglutinin (HA) and its cell surface receptor sialic acid (SA) to identify a B cell receptor (BCR) activation modality that proceeded through non-cognate interactions with antigen. Using a new approach to reconstitute antigen-receptor interactions in a human reporter B cell line, we found that sequence-defined BCRs from the human germline repertoire could be triggered by both complementarity to influenza HA and a separate mode of signaling that relied on multivalent ligation of BCR sialyl-oligosaccharide. The latter suggested a new mechanism for priming naïve B cell responses and manifested as the induction of SA-dependent pan-activation by peripheral blood B cells. BCR crosslinking in the absence of complementarity is a superantigen effect induced by some microbial products to subvert production of antigen-specific immune responses. B cell superantigen activity through affinity for BCR carbohydrate is discussed.
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    Publication
    Antigen identification and high-throughput interaction mapping by reprogramming viral entry
    (Springer Science and Business Media LLC, 2022-04) Dobson, Connor; Reich, Anna; Gaglione, Stephanie; Smith, Blake; Kim, Ellen; Dong, Jiayi; Ronsard, Larance; Okonkwo, Vintus; Lingwood, Daniel; Dougan, Michael; Dougan, Stephanie; Brinbaum, Michael
    Deciphering immune recognition is critical to understanding a broad range of diseases, and to develop effective vaccines and immunotherapies. Efforts to do so are limited by a lack of technologies capable of simultaneously capturing the complexity of the adaptive immune repertoire and the landscape of potential antigens. To address this, we present RAPTR (Receptor-Antigen Pairing by Targeted Retroviruses). RAPTR combines viral pseudotyping and molecular engineering approaches to enable one-pot library on library interaction screens by displaying antigens on the surface of lentiviruses and encoding their identity in the viral genome. Antigen-specific viral infection of cells allows readout of both antigen and receptor identities via single-cell sequencing. The resulting system is modular, scalable, and compatible with any cell type, making it easily implemented. These techniques provide a suite of new tools for targeted viral entry, molecular engineering, and interaction screens with broad potential applications.