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


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.

SUBMITTER: Moffett HF 

PROVIDER: S-EPMC6913193 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Moffett Howell F HF   Harms Carson K CK   Fitzpatrick Kristin S KS   Tooley Marti R MR   Boonyaratanakornkit Jim J   Taylor Justin J JJ  

Science immunology 20190501 35


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 w  ...[more]

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