Using CRISPR/cas9 gene editing for increased vaccine yields in avian cell lines
Virus production for vaccines is still a challenging issue, particularly with slow-growing viruses such as influenza. Many vaccines are produced in embryonated hen’s eggs or continuous avian cell lines. These cells have an inner mechanism, an antiviral immune response that tries to fight the infection and therefore inhibits the replication of viruses. However, when trying to grow viruses for vaccine production, this becomes a bottleneck in the manufacture of numerous vaccines. This project proposes to switch off this normal anti-viral mechanism to allow for more virus production.
Type level I interferons are proteins that protect cells from virus infection by switching on specific anti-viral genes. Among these are the interferon-inducible transmembrane (IFITM) genes. These proteins have been shown to inhibit the replication of several highly pathogenic animal and human viruses, including Ebola, influenza, and HIV-1. The implementing agency for this project, the Pirbright Institute, has shown that a reduction in the level of IFITM in chicken cells infected with influenza produce more virus than normal cells. This finding suggests that IFITMs have an important role to play in the control of viral infections and may be valuable in terms of vaccine production.
This project aims to generate cells lacking IFITM using gene editing techniques. It is believed that this approach will overcome a barrier in vaccine production, resulting in increased vaccine yields and reduced manufacturing time. This vaccine platform has the potential to reduce costs of production for many existing vaccines, thus enhancing vaccine availability for a wide range of livestock diseases important to smallholders in developing countries.
This project is funded through the Livestock Vaccine Innovation Fund, a partnership of the Bill and Melinda Gates Foundation, Global Affairs Canada, and IDRC. It represents a joint investment of CA$57 million over five years to support the development, production, and commercialization of innovative vaccines against priority livestock diseases in sub-Saharan Africa, South Asia, and Southeast Asia.