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Sci Immunol. 2019 May 17;4(35). pii: eaax0644. doi: 10.1126/sciimmunol.aax0644.

B cells engineered to express pathogen-specific antibodies protect against infection.

Author information

1
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N. Seattle, WA 98109, USA.
2
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N. Seattle, WA 98109, USA. jtaylor3@fredhutch.org.
3
Department of Global Health, University of Washington, 1510 San Juan Road, Seattle, WA 98195, USA.
4
Department of Immunology, University of Washington, 750 Republican St., Seattle, WA 98109, USA.

Abstract

Effective vaccines inducing lifelong protection against many important infections such as respiratory syncytial virus (RSV), HIV, influenza virus, and Epstein-Barr virus (EBV) are not yet available despite decades of research. As an alternative to a protective vaccine, we developed a genetic engineering strategy in which CRISPR-Cas9 was used to replace endogenously encoded antibodies with antibodies targeting RSV, HIV, influenza virus, or EBV in primary human B cells. The engineered antibodies were expressed efficiently in primary B cells under the control of endogenous regulatory elements, which maintained normal antibody expression and secretion. Using engineered mouse B cells, we demonstrated that a single transfer of B cells engineered to express an antibody against RSV resulted in potent and durable protection against RSV infection in RAG1-deficient mice. This approach offers the opportunity to achieve sterilizing immunity against pathogens for which traditional vaccination has failed to induce or maintain protective antibody responses.

PMID:
31101673
DOI:
10.1126/sciimmunol.aax0644

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