Biology subjects

Taylor, J. J.

Publications and source records attributed to Taylor, J. J..

2 recordsLinked to original sources

bioRxiv2019

B cells engineered to express pathogen-specific antibodies using CRISPR/Cas9 protect against infection

Effective vaccines inducing lifelong protection against many important infections such as respiratory syncytial virus (RSV), human immunodeficiency virus (HIV), influenza 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 utilized to replace endogenously-encoded antibodies with antibodies protective against RSV, HIV, influenza or EBV in primary human or murine B cells. The engineered antibodies were expressed in up to 59% of primary B cells under the control of endogenous regulatory elements, which maintained normal antibody expression and secretion. Importantly, a single transfer of murine B cells engineered to express an antibody protective against RSV resulted in potent and durable protection against RSV infection in immunocompromised hosts. This approach offers the opportunity to achieve sterilizing immunity against pathogens for which traditional vaccination has failed to induce or maintain protective antibody responses.

immunology↗

bioRxiv2019

Antigen-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 years 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. One-sentence summaryB cells edited by CRISPR/Cas9 to produce antibodies participate in humoral immune reactions and secrete neutralizing serum titers of anti-HIV bNAbs.

immunology↗