HIV-specific humoral immune responses by CRISPR/Cas9-edited B cells
-
- 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
Abstract
<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>
Journal
-
- Journal of Experimental Medicine
-
Journal of Experimental Medicine 216 (6), 1301-1310, 2019-04-11
Rockefeller University Press
- Tweet
Details 詳細情報について
-
- CRID
- 1360574094172081408
-
- ISSN
- 15409538
- 00221007
-
- Data Source
-
- Crossref