Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 216, Issue 6, Pages 1301-1310Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20190287
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Funding
- Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery grants [OPP1092074, OPP1124068, OPP1194977, OPP1146996]
- National Institutes of Health [1UM1 AI100663, R01AI-129795]
- Robertson Fund
- Cancer Research Institute Irvington Fellowship
- Bill and Melinda Gates Foundation [OPP1194977] Funding Source: Bill and Melinda Gates Foundation
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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.
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