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Antigen-specific humoral immune responses by CRISPR/Cas9-edited B cells

By Harald Hartweger, Andrew McGuire, Marcel Horning, Justin J. Taylor, Pia Dosenovic, Daniel Yost, Anna Gazumyan, Michael S. Seaman, Leonidas Stamatatos, Mila Jankovic, Michel C. Nussenzweig

Posted 26 Jan 2019
bioRxiv DOI: 10.1101/530832 (published DOI: 10.1084/jem.20190287)

A small number of HIV-1 infected individuals develop broadly neutralizing-antibodies to the virus (bNAbs). These antibodies are protective against infection in animal models. However, they only emerge 1 - 3 years after infection, and show a number of highly unusual features including exceedingly high levels of somatic mutations. It is therefore not surprising that elicitation of protective immunity to HIV-1 has not yet been possible. Here we show that mature, primary mouse and human B cells can be edited in vitro using CRISPR/Cas9 to express mature bNAbs from the endogenous Igh locus. Moreover, edited B cells retain the ability to participate in humoral immune responses. Immunization with cognate antigen in wild type mouse recipients of edited B cells elicits bNAb titers that neutralize HIV-1 at levels associated with protection against infection. This approach enables humoral immune responses that may be difficult to elicit by traditional immunization.

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