Accelerating recombinant protein vaccine discovery

Vaccination responses need to be rapid, efficacious and cost-effective if they are to outpace new viral threats emerging across the globe, says Jian He (Jason), Chemistry, Manufacturing and Controls (CMC) Head, WuXi Vaccines.

Technologies that hasten the pathway from vaccine discovery to commercialisation form an important part of the world’s ongoing quest to outpace emerging viral threats. Especially for rapidly-mutating viruses (such as SARS-CoV-2), tools that can help inform the rapid development of vaccines are crucial in being better prepared for future health crises.

Recent advances

The past few years have seen considerable advances in vaccine R&D, addressing the drawbacks of conventional experimental approaches, and exploring advanced adjuvants and delivery systems that improve vaccine efficacy and accessibility1. For example, early strategies for investigating new vaccine targets or developing formulations now increasingly rely on sophisticated computational approaches. A recent study published in Nature described the development of a new artificial intelligence (AI) tool that can predict new viral variants before they emerge2. The researchers suggested that if this tool had been deployed at the start of the pandemic, it would have accurately identified which variants of SARS-CoV-2 had the highest escape potential.

""

As a result of the pressures placed on the industry during the Covid-19 pandemic, timelines have already changed. While a typical chemisty, manufacturing and controls (CMC) timeline from DNA to Investigational New Drug (IND) application in 2015 would have been approximately 24 months, by 2023 the same pathway was expected to take only 10 months.

It is broadly acknowledged that hastening the pathway from vaccine discovery to commercialisation is not just desirable – it is an achievable step in defending humanity against future pandemics. In recognition of this, the Coalition for Epidemic Preparedness Innovations (CEPI) has set an aspirational 100-day mission to make a safe and effective vaccine against any virus3.

This would give more people much faster access to more effective vaccines. However, such achievements can only be achieved by leveraging research strengths, regulatory capabilities and technical platforms.

Adding automation

Recombinant protein vaccines, which are obtained by conventional genetic engineering, are based on the proteins of target pathogens that can activate our immune systems. Unlike other types of vaccines that use viral genetic codes or viral vectors, recombinant protein vaccines use only the antigenic proteins themselves. This means that they cannot cause disease and they generally do not need to be frozen for storage. Their efficacy, intrinsic clinical safety, easy storage and industrial production scalability has already positioned recombinant protein vaccines as the leading human vaccine technology. Today’s challenge is to make them as quickly and cost-effectively as possible.

A common challenge with recombinant protein vaccines is selection of the right antigen, or the product might be subject to long development cycles. Such challenges can be tackled by applying advanced technology platforms. In particular, a number of technologies now provide sufficient data to drive the change from manual to automation, and this can have a meaningful impact on the speed of vaccine development.

For example, applying automation and digitalisation to high-throughput process development and in-process testing platforms results in a faster and more systematic approach to purifying and verifying process samples, troubleshooting, and method optimisation. Automated liquid handlers can drive greater productivity, streamlined workflows and optimised assay precision and consistency, while automated buffer exchangers and customisable automated workflow equipment can give scientists access to high- throughput end-to-end solutions. Using these advanced technologies, better optimised cell line selection can expedite clone choice, while higher throughput screening and assessment, greater capacity to conduct parallel development, and automated cell line selection, cell culture and downstream development can all have significant impacts on timelines.

Open-access platforms

As well as investing in advanced technologies at individual facilities, another key learning from the pandemic was the tremendous value of collaboration. When organisations and countries work together towards a common goal, we can achieve much more than when we all just work in isolation.

Therefore, it is our vision that every vaccine can be made by building an open-access platform with the most comprehensive capabilities and technologies in the global biologics industry. An ability to draw on more open-access research knowledge and technical know-how, should allow us all to integrate high-quality, consistent healthcare in all corners of the world, ensuring that the populations of all countries have fair and equal access to life-saving vaccines.

Faster bioprocessing

Even once an effective vaccine has been developed and approved, significant challenges remain in manufacturing. This was particularly evident during the Covid pandemic, when vaccine production chains struggled to meet global demand due to insufficient numbers of biomanufacturing facilities, a lack of tech-transfer capability, inefficient arrangement of production stakeholders, and critical shortages in raw materials4.

Addressing these challenges involves the development of scalable processes at facilities with the capacity to produce the required volumes of vaccine. New modular and flexible manufacturing technologies bring important benefits. Compared with conventional stainless-steel bioreactor facilities, they offer a highly flexible, cost-competitive manufacturing strategy, ideally suited to the fluid demands of the vaccine market. These systems can be rapidly deployed for scaling up and scaling out to meet changing demands and different vaccine candidates.

Consistent and reliable supply chains have also become a key consideration. For recombinant protein vaccine developers, this includes access to effective GMP-grade adjuvants, which have been known to cause bottlenecks in production. Therefore, it is important for vaccine manufacturers to make sure they have a strong supply chain for these adjuvants, or the ability to produce their own.

Evolving industry

As recently as five years ago, contract development and manufacturing organisations (CDMOs) were not commonly used for the production of vaccines. However, the world’s vaccine manufacturing footprint has altered. While four leading vaccine companies still account for over 80% of the global market, these organisations found themselves with insufficient capacity during the pandemic. To address shortfalls, many of them engaged CDMOs for the first time.

Due to their innate agility and responsiveness to external pressures, CDMOs were able to ramp up capabilities for the production of large quantities of vaccines in a timely manner. Several CDMOs invested in new sites – or upgraded existing ones – to increase biotech capacities and reallocate resources.

Conclusion

Over the past few years, the vaccines industry has made a number of advances, but we must keep learning, collaborating and investing, to make sure we are prepared for the next global health emergency.

In particular, we must work to accelerate recombinant protein vaccine development. Frontline armaments in humanity’s future battle against the unknown must be large capacity biotech sites, equipped with the best available facilities, with automated high-throughput workflows and highly flexible, cost-competitive bioprocessing strategies. Broader uptake of these technologies will allow vaccination responses to be faster, more efficacious and more cost-effective, shortening the time it takes for them to reach patients and enabling us to be better prepared for future health crises.

DDW Volume 25 – Issue 1, Winter 2023/2024

References

  1. Tripathi T. Advances in vaccines: revolutionizing disease prevention. Sci Rep 2023;13:11748.
  2. Thadani NN, Gurev S, Notin P, et al. Learning from prepandemic data to forecast viral escape. Nature 2023;622:818-825.
  3. Delivering Pandemic Vaccines in 100 Days, 2022.
  4. Feddema JJ, Fernald KDS, Schikan HGCP, van de Burgwal LHM. Upscaling vaccine manufacturing capacity – key bottlenecks and lessons learned. Vaccine. 2023;41(30):4359-4368.

Jian HeAbout the author:

Jian He has 17 years of vaccine development with growing responsibilities in vaccine R&D and commercialisation of recombinant proteins, conjugates and VLPs in Merck & Co., WuXi Biologics, and WuXi Vaccines. He received his BS in Chemistry from Peking University, and PhD in Biochemistry from the University of Pennsylvania.

Related Articles

Join FREE today and become a member
of Drug Discovery World

Membership includes:

  • Full access to the website including free and gated premium content in news, articles, business, regulatory, cancer research, intelligence and more.
  • Unlimited App access: current and archived digital issues of DDW magazine with search functionality, special in App only content and links to the latest industry news and information.
  • Weekly e-newsletter, a round-up of the most interesting and pertinent industry news and developments.
  • Whitepapers, eBooks and information from trusted third parties.
Join For Free