To speed up flu vaccine development, A*STAR researchers have adapted HP-Q to purify viral particles for the first time.

Smoothing out kinks in vaccine production

16 Dec 2021

A new streamlined method for purifying lab-grown viruses could accelerate vaccine production, allowing manufacturers to respond rapidly to emerging viral threats

When a viral outbreak strikes, vaccines are our best hope for stopping their spread and saving lives. The expedited global rollout of COVID-19 vaccines, for example, has saved countless lives and continues to protect the vulnerable among us from potentially life-threatening infections.

Despite the progress we’ve made, viruses are sometimes one step ahead. Pathogens such as the influenza virus mutate rapidly, creating the need for new vaccine formulations annually to ‘retrain’ our immune systems to recognize and eliminate emergent viral strains.

The pressure to keep up with these elevated vaccine demands can be challenging for manufacturers. After all, commercial vaccine production are often lengthy, multi-step processes where viruses grown in cell culture systems must first be harvested and purified.

“There is a great need to develop efficient and simplified purification workflows to accelerate viral vaccine development and production,” explained Wei Zhang, Group Leader of the Downstream Processing Group (DSP) at A*STAR’s Bioprocessing Technology Institute (BTI). Presently, sluggish viral purification methods are a critical bottleneck in vaccine manufacturing. Even today, the gold standard flow-through anion exchange chromatography method requires multiple clean-up steps.

To rise above these barriers, Zhang and colleagues tested a newly-developed anion exchange platform, the NuviaTM HP-Q. Previously, this technology was found to enhance the purification of relatively larger proteins such as antibodies, however adopting the HP-Q for viral purification applications had, until now, never been explored.

Using H1N1—the virus responsible for seasonal flu outbreaks—as a model pathogen, the team created an optimized HP-Q protocol for viral purification. Promisingly, they found that the HP-Q resin displayed an excellent binding capacity for H1N1, capturing a high proportion of viral particles and effectively separating them from unwanted cell culture impurities.

Moreover, Zhang and colleagues found that they could eliminate steps upstream and downstream of HP-Q runs with no loss of efficiency. A single HP-Q chromatographic run was found to recover 70 to 80 percent of H1N1 proteins while simultaneously removing over 95 percent of residual host cell protein, without requiring comprehensive prior-purification sample preparation nor post-purification clean-ups.

According to Zhang, these exciting results could pave the way for faster, simpler and more cost-effective vaccine development and production, allowing manufacturers to be more agile and responsive in the event of an emerging viral threat. Ultimately, the team is confident that the benefits of the HP-Q can extend beyond the creation of flu vaccines.

“Although we use the H1N1 virus as the model product to establish the simplified HP-Q process for virus purification, this process could be adapted to the purification of other types of viruses, including [the] coronavirus,” remarked Zhang.

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Ta, D.T., Chu, K.L., Soonaan, N.I., Chin, C., Ng, S.K., et al.  A new and simplified anion exchange chromatographic process for the purification of cell-grown influenza A H1N1 virus, Separation and Purification Technology 263, 118412 (2021) | article

About the Researcher

Wei Zhang is a Staff Scientist and Group Leader of the Downstream Processing Group (DSP) at A*STAR’s Bioprocessing Technology Institute (BTI). Her team focuses on the downstream process development and product analytics of a variety of novel biotherapeutics, ranging from monoclonal antibodies, bispecific antibodies, viral vectors, and vaccines. Her team is also committed to working towards intensified and continuous downstream processing. Her team in BTI actively collaborates with biopharmaceutical companies and bioprocessing solution providers worldwide, including leading industrial players and local SMEs. Prior to BTI, Wei Zhang worked as a Staff Scientist and Project Lead at Codexis Laboratories Singapore, where she led a multidisciplinary research team to generate new industrial biocatalysts using directed protein evolution tools and develop bio-catalysis processes to produce high-value APIs.

This article was made for A*STAR Research by Wildtype Media Group