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

Area of Science:

• Immunology
• Genetic Engineering
• Virology

Background:

• Development of effective vaccines for lifelong protection against viruses like respiratory syncytial virus (RSV), HIV, influenza, and Epstein-Barr virus (EBV) remains a significant challenge despite extensive research.
• Existing vaccination strategies have limitations in inducing or maintaining durable protective antibody responses for certain pathogens.

Purpose of the Study:

• To develop an alternative strategy to traditional vaccination for achieving sterilizing immunity against viral infections.
• To engineer primary human B cells to express specific antibodies targeting RSV, HIV, influenza virus, and EBV using CRISPR-Cas9 technology.

Main Methods:

• CRISPR-Cas9 gene editing was employed to replace endogenously encoded antibodies in primary human B cells with targeted antibodies against specific viruses.
• The expression and secretion of engineered antibodies were analyzed to ensure they were maintained under the control of endogenous regulatory elements.
• An in vivo study using engineered mouse B cells demonstrated protection against RSV infection in RAG1-deficient mice.

Main Results:

• Engineered human B cells efficiently expressed and secreted targeted antibodies, maintaining normal cellular functions.
• A single transfer of B cells engineered to express an anti-RSV antibody conferred potent and durable protection against RSV infection in a mouse model.
• The genetic engineering approach proved successful in generating specific antibody responses.

Conclusions:

• This genetic engineering strategy using CRISPR-Cas9 to modify B cells offers a promising alternative for achieving sterilizing immunity against pathogens.
• The approach holds potential for diseases where traditional vaccines have been unsuccessful in providing lifelong protection.
• Further research may lead to novel therapeutic strategies for infectious diseases.