Disease X is coming. Are we ready?

Every great disaster movie begins with a scientist being ignored.

Lockdowns, face masks, no toilet roll or flour on the supermarket shelves – just like a zombie horror film. Such things are all becoming a more distant memory of the Covid pandemic.
Scientists estimate that we will face a pandemic or health emergency at least once every five years from here on, with some warning that we are no better prepared for a pandemic than we were in 2020. Experts say we need the UK government to invest in biomanufacturing infrastructure, infection-monitoring services, a more resilient healthcare system, better surveillance, and research to identify future threats. And we need this to be delivered at speed.

Back in 2021, as most of us still sat working from our bedrooms, kitchens and garden sheds, the astonishing feat of the development and authorisation of novel vaccines against covid in less than a year was hailed a triumph of scientific and technological innovation. However, despite the record-breaking timelines, globally more than 1.6 million deaths were reported before the first vaccine was approved for emergency use – at which point Covid was rampaging through almost every country of the world, at an unstoppable speed. Had a vaccine been available earlier, the social and economic devastation caused by the pandemic could have been lessened, if not avoided all together.

The sad thing is that many knew that a pandemic was coming way before the Covid virus exploded into our world. Scientists had been warning for years that we were on the brink of a pandemic, and the now-prophetic words can be found at the end of a research paper published in the journal Clinical Microbiology Reviews in October of 2007: “The presence of a large reservoir of SARS-CoV-like viruses in horseshoe bats, together with the culture of eating exotic mammals in southern China, is a time bomb.” Many other warnings from world renowned scientists followed, but unfortunately, outside of some members of the scientific community, there was little interest and no sense of urgency.

As we know, every great disaster movie begins with a scientist being ignored. And so, funding was not made available for vital research to commence – research that could have had us developing potential vaccines, and saved us months of development time, and thousands of lives, when covid hit.

The power of vaccines

Pandemic diseases affect us all. They do not respect borders. A virus that remains in circulation somewhere in the world is likely to spread and recur in other areas. The more widespread a disease is, and the larger and more varied the population it affects, the more likely it is to evolve more transmissible, more virulent and more vaccine resistant variants. Due to our global mobility, this means a disease starting in one location, can affect us all. And so, equitable vaccine distribution is essential in the fight against COVID-19, and future pandemics. Vaccines are one of our most powerful tools in the fight to outsmart pandemics. They can control the spread of viruses, reduce the chances of new variants emerging, prevent hospitalizations and ultimately save people’s lives.

Looking back – the UKs response to Covid
With the announcement from The World Health Organization (WHO) that Covid-19 no longer represents a “global health emergency”, what have we learnt, and are we more prepared now to act faster when facing the next Pandemic, to ensure we have the resilience we need to avoid a sequel to the Covid horror film.

When Covid hit, the UK Government soon realised they did not have the expertise internally to successfully navigate the pandemic storm. The UK Government Vaccines Task Force (VTF) was established in April 2020 by the then Government’s Chief Scientific Advisor, Sir Patrick Vallance, to drive forward, expedite and co-ordinate efforts to ensure that the UK population would have access to a clinically safe and effective vaccine against Covid. Dame Kate Bingham was appointed in May 2020 as chair of the VTF reporting directly to the Prime Minister – and was given three objectives; Secure access to the most promising vaccine(s) for the UK population as quickly as possible; make provision for international distribution of vaccines so that the benefits of UK leadership, and investment in this area could be widely shared; and establish a long-term vaccine strategy to prepare the UK for future pandemics.

Almost everyone in the UK will agree that the VTF’s strategy to build a diverse portfolio of vaccines across different platforms to give the UK the greatest chance of providing a safe and effective vaccine, was a huge success, with 85% of the UK population having received at least one Covid vaccination to date.

In terms of supporting the international distribution of vaccines, the UK worked closely with the Coalition for Epidemic Preparedness Innovations (CEPI) to establish the COVID-19 Vaccines Global Access facility (COVAX), early on during the pandemic. COVAX allowed rich countries to buy vaccines for poor countries, alongside buying vaccines for their own citizens. The UK Government made £548 million available to COVAX, including the commitment of supplying one billion vaccine doses to developing countries worldwide. In addition, the UK negotiated for temporary cease-fires in affected countries and facilitated distributing the vaccines for the people in those warzones.

Building UK pandemic resilience
At its outset, one of the most interesting and imaginative aspects of the VTF’s work lied in the plans it laid for future resilience and industrial leadership in this vital area. To do so, the VTF has provided targeted funding to accelerate and expand the UK’s ability to manufacture a range of vaccines at three sites, the Vaccines Manufacturing Innovation Centre (VMIC) in Harwell, the Cell and Gene Therapy (CGTC) site at Braintree and investment in Valneva in Livingstone.

So, where are we now, and what is the UK doing to ensure we are ready for disease X?

From Covid hitting to getting a vaccine approved took 326 days. Although this was an amazing feat, since vaccines usually take 3-10 years to develop and take to market, during this time, thousands of lives were lost, and world economies were flattened.

To avoid a delay in vaccine production in pandemic responses in the future, CEPI has articulated an aspirational goal: vaccines should be ready for initial authorisation and manufacturing at scale within 100 days of recognition of a pandemic pathogen – the ‘100-day challenge’. Coupled with improved surveillance providing earlier detection and warning, and with swift and effective use of non-pharmaceutical interventions such as testing, contact tracing and social distancing to suppress disease transmission, delivering a vaccine within 100 days will give the world a better chance of containing and controlling future pathogenic threats and averting the type of catastrophic global public health and socio-economic impacts caused by Covid.

As part of the 100-day challenge CEPI have stipulated that we must optimise manufacturing processes and maintain a network of warm manufacturing facilities, with reserved capacity for multiple different vaccine platforms. For anyone who works in the biopharma industry, they will know just how expensive it is to keep a facility running, and the option for having spare idle capacity is simply not a commercially viable option. Therefore, maintaining several government owned manufacturing facilities, specifically for pandemic preparedness would cost the taxpayer an exorbitant amount of money. Therefore, the government’s long-term vaccine strategy to prepare the UK for future pandemics, has evolved to focus on partnering with the bioindustry to jointly develop the capacity and capabilities needed.

Since Covid, and with the high costs of maintaining biomanufacturing facilities, VMIC has been sold by the Government to Catalent to ensure it does not lose its ability to develop new vaccines. Catalent plans to invest up to £120 million to complete the building of the facility and equip it with state-of-the-art capabilities for the development and manufacture of biologic therapies and vaccines, including mRNA, proteins, and other advanced modalities. It is expected that the new facility will employ more than 400 people and support public and private organizations seeking to develop and manufacture biotherapeutics.

CGTC’s Braintree site was originally funded in 2020 with £127 million by the UK Government to provide flexible GMP-qualified manufacturing innovation facilities specifically for powering the pandemic vaccine manufacturing. In the end there was no vaccine to be manufactured at the Braintree site due to the success of the AstraZeneca, Pfizer and Modern vaccines, but significant progress has been made and the fully operational site will be online by 2025 and will work in partnership with the industry to develop and manufacture biologics and viral vector vaccines.

CEPIs 100-day challenge also has several overarching scientific and technological prerequisites to enable success, many of which rely on the construction of new research, development, and manufacturing facilities – and all required on an accelerated timescale. Core to success is the deployment of modern methods of construction, where offsite manufacturing dominates, enabling buildings to be completed in less than half the time of traditional construction.

Based in Northumberland, Merit, an industrialised construction, and manufacturing specialist focussed on the design, manufacture, build and validation of advanced manufacturing facilities, are pivotal in the UK’s response to the 100-day challenge.

The 100-day challenge requires the creation of libraries of vaccine constructs against viruses with the greatest pandemic potential and build significant platform experience that could be leveraged for rapid adaptation in an outbreak. On this front, the UK has started its journey, with the Government funding the £multi-million CPI mRNA Centre of Excellence in Darlington, providing the UK with the capability to develop and manufacture lipid nanoparticle encapsulated messenger and self-amplifying RNA vaccines, and ultimately creating a ‘vaccine library’. The vaccine library will form the basis of a rapid response facility, which will enable mRNA vaccines to be developed to help protect against new variants of COVID-19, as and when they emerge. The facility was built by Merit at pace, and the modular nature of the building enables the facility to be quickly increased in size to cope with emerging pandemics or infectious disease threats if required. Merit was awarded the contract following competitive tender, offering a solution of 32 weeks from process layout approval. Using Merit’s UltraPOD® product-based solution, a fully offsite manufactured POD building enabled fast track delivery of this health critical project. The new mRNA facility has the same quality and feel as a traditional build.

Alongside the vaccine library, to be successful with the 100-day challenge, we need to establish global clinical trials network, including laboratories, establishing early biomarkers of robust immune response. On this front, again, with the help of Merit, the UK is making progress, with the new Government funded Moderna Innovation and Technology Centre (MITC) being established at Harwell Campus in Oxfordshire. Successful completion of the MITC enable the production of UK-made mRNA Covid-19 jabs for the next 10 years. The MITC includes a clinical biomarker laboratory that is being constructed by Merit- and the firm’s innovative proprietary integrated platform technology means it will be operational in just 12 months’ time. The product-based solution provides a right first time, pre-validated MHRA approved facility – where validation is achieved in days, rather than months.

Looking forward – UKs future pandemic preparedness
These significant investments from the UK Government are preparing us well for the next pandemic and enabling the journey to be able to produce a vaccine in under 100 days. However, some have criticised the Government for investing heavily in mRNA technologies at the expense of other vaccine platform technologies.

mRNA is not going to be the solution to every vaccine needed – in part because some vaccine targets are not proteins, but carbohydrates, and you can’t encode those in genetic material. The development of the technologies underlying current adenovirus and mRNA vaccines took decades. A key reason why Covid vaccines were developed so quickly was because scientists had already spent years studying the spike proteins from MERS (Middle East respiratory syndrome) and seasonal coronaviruses and learnt how to universally stabilise these proteins for vaccine development.

In addition, we must realise that future pandemic threats are not just corona viruses. In recent years, we have seen emergences and re-emergence’s of numerous other human infectious diseases such as Monkey Pox, Ebola, Lassa fever, chikungunya, Zika, and epizootic avian influenza. Each pandemic threat or neglected disease pathogen has its own unique vulnerability to acquired immunity, and it is not yet possible to predict which technology might achieve the highest levels of protective immunity or can be produced easily at scale. Therefore, capacity for developing, manufacturing, and delivering several vaccine technologies must be maintained. Experts are warning that consideration should be given to secure bulk antibody manufacturing capability and nimble plant antigen manufacture – both critical parts of the UK’s biosecurity and future pandemic armoury to support a rapid response to future disease outbreaks – which the VTF identified as a potential weakness in the UK’s future pandemic response, as well as a surprising gap for a country as focused on the life sciences industry as the UK.

This time round, the government is listening to the scientists, and is now working with industry to understand the current state of the UK’s vaccine manufacturing resilience. They recently launched an industry survey to ascertain the capabilities and capacities of the UK bioindustry in terms of pandemic resilience, and significant investments were announced just last week, with the launch of the £38million Biomanufacturing Fund, in capital grants to incentivise investment in the manufacture of vaccines and biotherapeutics, to improve the UK’s health resilience for future pandemics.

The announcement of the new government investment will help develop health resilience in the UK for future pandemics through increased domestic capacity, by providing flexible capabilities that can be re-deployed in health emergencies.

Maintaining robust vaccine research, development, and manufacturing capabilities should be a cornerstone of any national security strategy. Cultivating such a complex infrastructure requires long term funding and political backing. It is great to see that the UK Government is now listening to the scientists, and is acting now, to establish, at pace, a series of warm standardised manufacturing facilities, for multiple different platforms, which could be activated within days or weeks to produce vaccines in response to a future pandemic outbreak – including mRNAs, viral vectors and protein vaccines.

Utilising this approach means another blockbuster pandemic horror film is unlikely to make it into production.