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  • HIV-specific humoral immune...
    Hartweger, Harald; McGuire, Andrew T; Horning, Marcel; Taylor, Justin J; Dosenovic, Pia; Yost, Daniel; Gazumyan, Anna; Seaman, Michael S; Stamatatos, Leonidas; Jankovic, Mila; Nussenzweig, Michel C

    The Journal of experimental medicine, 06/2019, Letnik: 216, Številka: 6
    Journal Article

    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 yr 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 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.