Affinity Precipitation Purification of Virus-Like Particles

This project proposes to develop an affinity precipitation process for selective, non-chromatographic separations of viruses and virus-like particles (VLPs).

Industry Need

Virus-like particles (VLPs) are widely used as vaccines for a wide range of diseases, including COVID-19, and as vectors to deliver therapeutic genes in gene therapy.
Although some separation steps following cell culture to produce VLPs are simple and effective (e.g., using filtration), chromatography—which selectively binds the product to porous particles, rather than impurities—is often still favored for its high selectivity.
Chromatography of viruses and similar particles is complicated and limited, relative to that of therapeutic proteins, by the slow transport in and partial or complete exclusion from the pore space of chromatographic particles and low recoveries due to strong binding.
Efforts to address these issues have included extensive experimental studies, but the operations are still inherently inefficient, making scale-up to the levels required for high-volume production a challenge, especially to the extent that future implementations may include continuous modes of operation.

Solution

The University of Delaware will develop an affinity precipitation process for selective, non-chromatographic separations of viruses and VLPs.

In affinity precipitation, the product is driven to associate with itself in the liquid, rather than binding to solid particles. This investigation will use affinity precipitation for adenovirus (AdV) capture as a non-chromatographic alternative that combines the high selectivity of a chromatography-like affinity system with the operational benefits of working entirely within liquids.

Outputs/Deliverables

Design and expression of an affinity ligand/precipitant complex and a model target structure for studying VLP affinity precipitation

Preparation of sufficient materials to enable batch measurements and exploratory continuous operation of affinity precipitation characteristics

Setup of a continuous flow affinity precipitation system to allow operation using very small quantities of materials

Impacts

The successful completion of the proposed project will allow the inclusion of an adaptable, efficient step in future manufacturing processes for a class of vaccines against a novel coronavirus.

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Project Lead

University of Delaware