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

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 lev...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547862/
https://www.ncbi.nlm.nih.gov/pubmed/30975893
http://dx.doi.org/10.1084/jem.20190287
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author 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.
author_facet 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.
author_sort Hartweger, Harald
collection PubMed
description 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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spelling pubmed-65478622019-11-06 HIV-specific humoral immune responses by CRISPR/Cas9-edited B cells 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. J Exp Med Research Articles 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. Rockefeller University Press 2019-06-03 2019-11-04 /pmc/articles/PMC6547862/ /pubmed/30975893 http://dx.doi.org/10.1084/jem.20190287 Text en © 2019 Hartweger et al. https://creativecommons.org/licenses/by-nc-sa/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
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.
HIV-specific humoral immune responses by CRISPR/Cas9-edited B cells
title HIV-specific humoral immune responses by CRISPR/Cas9-edited B cells
title_full HIV-specific humoral immune responses by CRISPR/Cas9-edited B cells
title_fullStr HIV-specific humoral immune responses by CRISPR/Cas9-edited B cells
title_full_unstemmed HIV-specific humoral immune responses by CRISPR/Cas9-edited B cells
title_short HIV-specific humoral immune responses by CRISPR/Cas9-edited B cells
title_sort hiv-specific humoral immune responses by crispr/cas9-edited b cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547862/
https://www.ncbi.nlm.nih.gov/pubmed/30975893
http://dx.doi.org/10.1084/jem.20190287
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