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Development of a Downstream Process for Complex Vaccines - From Bench to Clinical Manufacturing
(Seminar/Conference)
Dr. Xun Liu
Director, Downstream Process Development
Vaccine Production Program Laboratory
VRC/NIAID/NIH
Abstract
Western, Eastern and Venezuelan Equine Encephalitis Viruses (WEVEE) are alphaviruses in the Togaviridae family. These alphaviruses are highly infectious with severe, long-term neurological effects and varying levels of mortality. In addition, they constitute an ongoing bioterrorist threat. The VRC is developing a trivalent virus-like particle (VLP) vaccine for the WEVEE alphaviruses. The enveloped VLPs are replication deficient and are formed in vitro through the expression of the structural proteins of each virus.
Production of alphavirus VLPs are challenging as the VLPs are intrinsically lytic to the expression cells in culture. Therefore, generation of stable cell lines for VLP production has not been possible with techniques commonly used for cell line development. To develop a Phase I clinical product, a PEI-based transient gene expression platform process has been developed and scaled-up to 50L using completely disposable upstream equipment. Purification of VLPs that meet purity and quality criteria for human clinical use has been difficult due to the complexity of the VLP, structural stability, and level of expression. However, a robust downstream platform process has been developed that is used for all three VLP strains. The Phase I process has been finalized and transferred for GMP manufacturing. Background and process optimization data for our Phase I manufacturing process of these vaccines will be presented.
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(540) 231-0680