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

DOI Web Site 被引用文献1件
  • Harald Hartweger
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 1
  • Andrew T. McGuire
    Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 2
  • Marcel Horning
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 1
  • Justin J. Taylor
    Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 2
  • Pia Dosenovic
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 1
  • Daniel Yost
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 1
  • Anna Gazumyan
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 1
  • Michael S. Seaman
    Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 5
  • Leonidas Stamatatos
    Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 2
  • Mila Jankovic
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 1
  • Michel C. Nussenzweig
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 1

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<jats:p>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 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.</jats:p>

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