Development of a platform for the purification of viral vector systems for the manufacture of vaccines and gene therapies

Cell and gene therapies (CGTs) and novel vaccines are an emerging, rapidly growing area due to their potential to address unmet medical needs.  The FDA expect 10 products a year to be approved by 2025.  Ireland is well-positioned to expand its manufacturing capabilities into this exciting area. 

Production of CGTs and vaccines is in its infancy when compared to biopharmaceuticals.  There are several manufacturing challenges to be overcome in order to ensure reliable supply at an affordable price.  One of the major stumbling blocks is the development of a scalable platform-based approach to downstream processing.

Viral particles, produced using modified viral vectors, are one of the principal platforms used for vaccines and gene therapies. While much work has been progressed on upstream production of these particles, their downstream purification is far less developed. This project aims to develop systematic approaches for the design, optimization and scale-up of viral particle purification using chromatography.

Chromatographic purification of viral particles is based on the surface properties of the viral particles or their size with, typically, a combination of at least two steps required to deliver effective purification.  There have been numerous published reports of chromatographic applications demonstrating the high potential of chromatography as a purification platform for viral particles.  The specific applications vary regarding the type of chromatography resins (ion exchange, affinity, size exclusion, hydrophobic interaction etc.), the mode of operation (bind and elute or flow-through) and the format of the resins (packed bed, monolithic, membrane absorbers etc.).  In all cases, the lack of a systematic design approach makes efficient and reliable process development difficult to achieve.

In this project, it is proposed to investigate the development of a platform approach to the design and scale-up of chromatography operations for large-scale purification of viral particles for vaccine and gene therapy applications.

Project funding: IRC Employment-based Postgraduate Scholarship Scheme in conjunction with APC

PhD Researcher: Alexandra Bogdanovic

PhD Supervisor: Jessica Whelan, Susan McDonnell