In August 2023 the announcement of the newly unveiled Vaccine Development and Evaluation Centre in the UK provoked consternation on social media. Repeated reference to the threat of “Disease X” was identified and questioned. Disease X is the term used to describe the future threat presented by a currently unknown pathogen. Understandably, the public is susceptible to misinformation around this mysteriously named concern. However, the accurate information is out there and a quick google search can offer insight into what Disease X is, and how and why scientists are already preparing for it.
What’s in a name?
The rather science-fiction-sounding name was adopted by the WHO in 2018 for its list of priority diseases. WHO suggests that Disease X “represents the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease”. It can be considered, therefore, akin to the familiar algebraic foe “x”, representing the variable or unknown.
What will it be?
Disease X is “supposed to be caused by a pathogen X”, which itself is expected to be a zoonosis. It is predicted to emerge from an area where the “right mix of risk factors highly promotes the risk for sustained transmission”. If this all sounds terribly hypothetical or broad, it is. Indeed, CEPI states that 25 viral families are known to infect humans, and over 1.6 million undiscovered viral species within them are estimated to exist in mammal and bird hosts.
However, Johns Hopkins Centre for Health Security suggests that 6 viral families capable of infecting humans (Adenoviridae, Coronaviridae, Orthomyxoviridae, Paramyxoviridae, Picornaviridae, and Poxviridae) have the following key traits to enable a pandemic:
- No immunity (no preexisting immunity in the global population)
- Airborne (spread via respiratory transmission)
- Silent (transmissible by infected people without symptoms)
- Harmful (without existing, effective therapeutics or vaccines)
If we don’t know what it is why are we preparing?
It might seem a bit hopeless to prepare ‘blindly’ for an unknown threat, but the need is great; infectious disease outbreaks now occur 3 times more frequently than they did 40 years ago. Furthermore, our experience with the COVID-19 pandemic and increasing outbreaks of diseases like mpox should demonstrate the importance of preparation. In fact, although we may have seemed tragically underprepared to meet COVID-19, the vaccine community set a record timeline of 326 days between discovery of the virus to the first emergency use of the vaccine.
Another lesson from the pandemic is how much damage can be done before a vaccine is ready, and even while it is being deployed. Thus, the need to arm the world as quickly as possible is a cause championed by many, including CEPI. CEPI outlined an ambitious goal to this end in 2022:
“Vaccines should be ready for initial authorisation and manufacturing at scale within 100 days of recognition of a pandemic pathogen, when appropriate.”
The hope is that, alongside “improved surveillance” and “swift and effective use of non-pharmaceutical interventions”, this goal would give us a better chance at “containing and controlling” future threats. CEPI’s Tom Mooney, Senior Communications and Advocacy Manager emphasises that this will require “the right level of financial commitment and political will” but is a “[credible] aim to eliminate the risk of epidemics and pandemics”.
How are we preparing?
If the 100 Days Mission is the guide, how is the vaccine community stepping up to the plate? CEPI outlines several stages: readiness, reaction, and rollout and review. Within these stages, CEPI is advocating the development of a “vaccine library” and is supporting the development of novel technologies with dedicated funding.
A vaccine library comprises prototype vaccines created for each of the key virus families, and CEPI is prioritising the development of vaccine libraries for up to 10 high-risk virus families. These families are identified through potential for outbreak transmission or zoonotic spillover, ability to mutate, and mode of transmission among other factors. Within these families, vaccine candidates will be created for up to 15 different viruses depending on the complexity of the family.
The vaccines in each library will be based on “rapid-response platforms”. These are systems that can be adapted for use against different pathogens through insertion of new genetic or protein sequences.
“Building vaccine libraries is a mammoth task requiring major investment, so we anticipate it being a shared global project with CEPI playing a pivotal leadership and connecting role.”
Other areas of focus for the vaccine community include establishing or improving manufacturing capabilities and ensuring that vaccine development is executed with access in mind. One of the unfortunate lessons of the COVID-19 pandemic, and indeed mpox, has been that equity was not the political priority it should be.
Access is key
The Lancet’s Aimee Ramgolam reflects on the COVID-19 pandemic in an article on Disease X, emphasising that “on a global scale, sharing is integral to preventing the proliferation of a pandemic”. This is easier collectively agreed upon than collectively enacted. Ramgolam recognises that elected officials “will always act in their own country’s best interests”, so we would be better using our time “making collaborative working politically beneficial to individual countries”. Thus, governments would find incentive to share.
An example of effort to address this is presented by Ramgolam: WHO’s pandemic treaty. This would be a potentially legally binding agreement aiming to address the following key gaps:
- Global preparedness and response arrangements
- Sustained, predictable funding for health emergency preparedness and response
- Governance and oversight mechanisms
Local manufacturing is also an area for development; we know that in 2021 Africa imported 99% of its vaccines. Going forward, Africa CDC and the African Union have set the goal of manufacturing, producing, and supplying over 60% of the total vaccine doses on the continent by 2040. How will this happen? Through the efforts and collaborations of organisations like Afrigen, led by Professor Petro Terblanche, Africa will should be able to “innovate with the world”. However, greater investment and policy reform are still needed.
Politics and pounds
The key drivers of preparation for Disease X are political will and financial investment. These often come together, or not at all. So, how can we encourage them? If, as Ramgolam suggests, elected officials are guided by their voters, a first step could be to educate the voters on the significance of Disease X, not by fear mongering, but by setting out the available facts and contrasting threats with tools.
It’s taken us this long to mention Kate Kelland, author of Disease X: The 100 Days Mission to End Pandemics purely because we focused on freely available information online. However, in an interview with the World Economic Forum’s Radio Davos Podcast host Robin Pomeroy, she gave an insight into some of her recommendations. Relating to financing, she calls for a “pandemic fund already set up and populated with actual money” before it is needed. For political leaders, there is a need to balance “low-regret decisions” with greater risks:
“If you delay, you will almost certainly be too late.”
If you made it this far, don’t forget to subscribe for more like this. If you are interested in Disease X, check out our World Vaccine Congress agenda for Barcelona, featuring a “Biothreats and Disease X” workshop. We hope you will join us there!
