Dr Leonardo Magneschi is the Head of Molecular Biology at Ingenza. In 2020 he and his team embarked upon a project in conjunction with the University of Oxford and the Centre for Process Innovation (CPI) to rapidly formulate a highly effective vaccine against SARS-CoV-2, the virus responsible for the COVID-19 pandemic. New research published in Science by Caltech shows that this innovative coronavirus-fighting technology has the potential to provide protection against future novel SARS-CoV-2 variants and as-yet-undiscovered coronaviruses that could transfer into the human population in the future. In this blog, Leo describes his experience of participating in the development of this crucial vaccine and his team’s ongoing research in this ever-changing field. He also highlights the unique skills Ingenza has brought to the table throughout these ground-breaking programmes that have allowed them to proceed full steam ahead.
Developing a vaccine that’s accessible to all
In April 2020, the CPI recommended that the University of Oxford contact us for help with moving its new COVID-19 vaccine candidate from mammalian cells to microbial platforms. The motivation behind this was predominantly speed and cost; the turnaround time of mammalian cell-culture systems are too slow to keep pace with the potential mutations of SARS-CoV-2, and the media required to grow enough mammalian cells to manufacture vaccine at a sufficient scale would make it cost prohibitive for worldwide distribution. Microbial systems are far more cost efficient, and have the potential to make the overall cost of the R&D process – as well as the final vaccine manufacture – more affordable, ensuring equitable vaccine access globally. Although we initially didn’t receive funding for this project, we truly believed in the science behind this revolutionary technology, and its potential to impact the trajectory of the pandemic in countries unable to afford the first wave of vaccines being developed. We accepted the challenge and began working right away, doing what we do best: engineering microbes and developing processes for efficient and sustainable biomanufacturing.
Quite early on, we were able to scale up production by moving the candidate to a microbial system, making the end product an estimated 10 times cheaper than other COVID-19 vaccines on the market, with no requirements for storage in freezers and the ability to induce strong neutralising antibody responses. This made the new vaccine a promising option for countries that couldn’t afford the other options that were available to them, and a good booster option for countries that had been offered vaccine doses earlier on in the pandemic.
For me, the SARS-CoV-2 virus almost seemed like an enemy that we had to defeat. The Ingenza team is very international, with colleagues coming from 16 different countries, and for many of us lockdown and travel restrictions also meant being separated from our families and partners for a significant length of time. It was really fulfilling to work on something that was going to help the whole situation, especially as many of us felt quite helpless at the time, and we all put a lot of energy into finding a solution that would produce a cost-effective vaccine against a deadly disease. The whole process was enormously rewarding for me on a personal level.
Standing on a rich knowledge base
Ingenza has a huge wealth of diverse experience and transferable skills from all aspects of the life sciences and chemistry sectors, and this enabled us to quickly coordinate efforts between our molecular biology and fermentation teams in response to the emerging pandemic. We had the major advantage of our unique inGenius CMC platform encompassing our upstream and downstream bioprocessing and genetic engineering expertise across several different microbes, which undoubtedly gave us a head start. That meant we could jump right in and build on our solid foundations of prior knowledge to rapidly prove that the new vaccine was functional in principle, and then focus on optimising the system for proper scalable manufacturing.
Developing a vaccine is certainly a far cry from my original background, but I soon realised that we were actually using the same tools we were already familiar with, just for a slightly different purpose. This whole experience has shown us that we have a huge and versatile skillset that we can use to approach anything that our clients throw at us, whether it is addressing challenges in human health or sustainable manufacturing. We all learned so much in a very short space of time, and this ability to adapt was vital to our rapid progress.I don’t think words can describe how privileged I feel to be leading such a brilliant team!
A defence against an evolving threat
Many COVID-19 vaccine candidates work by presenting fragments of the SARS-CoV-2 spike protein (known as the receptor-binding domain, or RBD) to the body to generate an immune response. However, newly arising SARS-CoV-2 variants, such as various forms of Omicron, are increasingly able to evade the original vaccine’s immune response due to mutations in the changeable regions on these RBDs.
That’s why the consortium has now begun a new venture to develop a new vaccine that will give immunity against any known and future strains and variants simultaneously. The principle behind this is to direct the immune response to the parts of the RBD that are shared by viruses in the SARS-like Betacoronavirus family, and in particular all Sarbecoviruses. Ingenza is once again key in engineering the microbes that will be used in the development of this vaccine and producing something that can be manufactured beyond lab scale for commercial use. The project has received funding from the Coalition for Epidemic Preparedness Innovations (CEPI) in summer 2022 and, with this support, we are now working towards establishing first-in-human clinical proof of concept.
Although the height of the pandemic has hopefully now passed, we know how important it is to continue with the development of this broader-spectrum vaccine because of its potential value in the future. We have essentially switched focus to preparing for any upcoming pandemics caused by the subgenus Sarbecovirus, which is the most likely virus to make the jump from animals to humans. A large part of this future-readiness is producing an affordable vaccine that could provide people all over the world with an accessible defence against a potentially deadly disease.
Maintaining momentum through conversation
Transparent and effective communication has been key throughout this whole project, and we have frequent discussions with all members of the consortium, as well as internally at Ingenza. There are a lot of moving parts involved, so maintaining close contact between the different departments at Ingenza and partner organisations is crucial for staying on top of our work and reaching the end goal as a team as quickly as possible. It feels great to be collaborating with several prestigious institutions and gaining more international exposure.
There is still some way to go with this new vaccine before it will be widely available, but we have been moving ahead very quickly thanks to the combined expertise of all parties. Ingenza is looking forward to continuing the collaboration and to successfully helping to bring this vital product to market at some point in the not-too-distant future.