The Coalition for Epidemic Preparedness Innovations, CEPI, was launched in 2017, in the wake of an outbreak in west Africa of Ebola. The virus causes internal bleeding, inflammation and tissue damage, killing around half the people it infects.
Now CEPI has launched a $3.5 billion plan to reduce the future risk of pandemics, potentially averting millions of deaths and trillions of dollars in economic damage.
There are many facets to CEPI’s $3.5 billion strategy, which aims to help the world cut vaccine development timelines for new pandemics by two-thirds, to just 100 days.
I talked about this ambitious plan with Richard Hatchett, CEPI’s Chief Executive Officer. His edited responses are shown below.
WHAT DID WE LEARN FROM COVID-19?
Our response to the pandemic — in terms of surveillance, how we’ve used testing and tracing, how we’ve used non pharmaceutical interventions — is revelatory when it comes to the ways in which the world was utterly unprepared, except in some small pockets, to respond really effectively.
It has also shown what we might achieve through science.
CEPI is thinking about how the world needs to be organised and the opportunities that science presents, drawing on lessons learned and observed during the COVID-19 pandemic.
We’re reflecting on what we’ve experienced, the successes that we’ve had and the challenges that we’ve encountered.
We now have the tools that we believe — if coupled with investments in preparedness and advancements in regulation — could get vaccine development down to 100 days from encountering a pandemic threat.
HOW CAN YOU SPEED UP VACCINE DESIGN?
One concept that I believe will be really critical for future preparedness was first fully articulated by scientists at the National Institutes of Health, in Bethesda, Maryland.
Their idea is to look across the roughly 260 viruses that we know can cause human disease which come from 26 or 27 different viral families of concern — you can even rank the viral families by pandemic potential — and solve the problems of vaccine development of the most concerning viral families in advance using what they refer to as “prototype pathogens”.
This is what had been done with the SARS and MERS coronaviruses and it is only because this work had been done that we were so ready to jump on the related coronavirus (SARS-CoV-2) that causes COVID19 when it emerged at the end of 2019.
We’ve embraced this approach and are proposing to create “prototype” vaccines against important families of viruses, to speed up vaccine development in case of emergency.
We could also develop these prototypes using approaches (so-called “vaccine platforms”) that lend themselves to rapid response in the future.
Each platform allows for “plug in and play” vaccines, where you start with a platform, an underlying vaccine approach that you’re familiar with, that you have worked out, that you understand how to manufacture, and for which you already have a great deal of information about its safety.
Then, in response to a pandemic threat, you just drop in the genetic code of the target of interest from the new virus and off you go.
In short, we need to produce a library of prototype vaccines and other biological interventions against representative pathogens from critical viral families.
The good news is that we already have vaccines against diseases representing 15 of the viral families, which means a big chunk of the work has already been done.
The problem is that except in the case of coronaviruses we haven’t translated those vaccines from slow platforms, which would take a long time to replicate for a new pathogen in an emergency, over to the fast platforms that will let us move quickly.
WHICH PANDEMIC VACCINES SHOULD WE PRIORITISE?
The most obvious — really blindingly obvious — is influenza.
We have only partially modernised our influenza vaccines. We have recently developed protein-based influenza vaccines but that kind of vaccine has not proved — in the response to COVID-19 — to be as rapid as the viral vector (Oxford-AstraZeneca approach) or the mRNA approach (Pfizer-BioNTech and Moderna).
The other problem is that for much of our influenza vaccine manufacturing we still rely on vaccine components that are grown in chicken eggs.
This technology is reliable, which is why we’ve continued to use it, but it doesn’t scale very easily and there is not really any way to compress the development time (Tom Frieden, the former director of the US CDC, once asked ‘What do you want me to do? Yell at the eggs?’).
And if we had a serious influenza pandemic, just using eggs we wouldn’t be able to make enough vaccine for the world, which would be a catastrophe. So, there’s still work to do on influenza.
Another example that I’m particularly concerned about remains the coronaviruses.
We have cracked them partially, but we’re now thinking about whether broadly protective coronavirus vaccines, that protect against multiple coronaviruses, are scientifically feasible — if they were, that would be really important and perhaps let us take coronaviruses off the table.
The reason so many of us were concerned about coronaviruses prior to COVID-19 is that within the coronavirus family, there are viruses as transmissible as a common cold, and as lethal as MERS which has a 35% mortality rate.
Prior to COVID-19, what we hadn’t seen yet were viruses that combined these traits, and of course COVID-19 which falls somewhere within the range of a 0.5% mortality rate, is far from the worst case, obviously.
The emergence of the highly mutated Omicron variant – which I discussed at the World Health Assembly special session this week – reminds us that the coronaviruses are really protean and still present a massive, unpredictable threat to global populations.
There is also the family of viruses known as paramyxoviruses, some of which have R (reproductive numbers) that make the Delta coronavirus look slow.
The family includes mumps, which has a reproductive number of 10 to 12 (Delta is five to eight), and measles, which is around 12 to 18, as well as the Nipah and Hendra viruses, which belong to a different genus within the paramyxovirus family and have an extremely high fatality rate in the 50-80% range.
One even appears in the Hollywood movie Contagion (2011), MEV-1, the film’s fictional virus, is modelled upon the bat-borne Nipah and underlines how over history, many deadly viruses have jumped from one species to another — from birds to people, or from pigs to people or from birds to pigs to people.
HOW DID THIS PROTOTYPE VACCINE APPROACH WORK FOR COVID-19?
The scientific community had already done important developmental work to understand how to make vaccines against coronaviruses before the emergence of SARS-CoV-2 that causes COVID-19.
In fact, it was the only viral family that we had done this for in a systematic way on rapid response platforms, and we had done this because of our prior experience with severe acute respiratory syndrome (SARS-CoV-1) in 2003, and Middle East Respiratory Syndrome (MERS) in 2013.
Thanks to earlier research, the scientific community understood the target of the vaccine and the Vaccine Research Centre at the US National Institute for Allergy and Infectious Diseases had done work to optimise the spike protein on the MERS coronavirus — the protein which enables it to invade human cells — to make it lock into the right shape to be more a more potent immunogen, to make it trigger a better protective immune response.
This method of stabilising the spike protein in what is called its “prefusion form” — its shape before it docks with a human cell — was not developed originally for coronaviruses but came from years and years of work on HIV and on Respiratory Syncytial Virus (RSV).
RSV didn’t yield to vaccine approaches until researchers understood that they had to stabilise the prefusion form of the corresponding protein on the RSV. Before this, they had tried to develop vaccines through other techniques and kept encountering failure after failure.
Vaccine designers were able to use that knowledge instantly, once they had the sequences of the new virus.
Similarly, Oxford had developed a vaccine for MERS on its ChAdOX viral vector platform that already entered human clinical trials.
The team at Oxford pivoted instantly to take what they had learned from MERS and apply it to developing a COVID-19 vaccine and then subsequently they paired up with AstraZeneca to share this vaccine with the world.
USING THIS PROTOTYPE, HOW QUICKLY COULD VACCINE MAKERS REACT TO COVID-19?
The NIH and the US company Moderna were able to design their RNA vaccine within about 48 hours of getting the genetic sequences of the new coronavirus and their vaccine was subsequently shown to be 95% effective and very safe.
They were quick because they didn’t have to worry about working through the vaccine design issues and making sure they had the right target and making sure that target was optimised. That work had already been done.
They then went directly into essentially manufacturing and testing the vaccine, which is where CEPI jumped in.
We funded Moderna to develop clinical trial material, just 12 days after the genetic sequences were released, and the work we funded was manufacturing material for the clinical trials. They were in clinical trials 66 days after the sequences were released.
After that great head start, they then went through a fairly conventional, if highly accelerated, approach to development, including phase one, phase two, and phase three clinical trials.
HOW DO YOU SPEED UP VACCINE TESTING?
The second component of our 100-day mission is to dramatically compress the actual development, testing and release of new vaccines when you’re encountering a disease that’s truly new, that you haven’t seen before.
That response has to be ready to move quickly and with maximum efficiency once a new threat emerges.
Ultimately, the regulators have to be prepared, in the right risk-benefit context, to adopt a different paradigm of regulating emergency vaccines.
You can see elements of this preparation in what we did in 2020.
The UK’s MHRA (Medicines and Healthcare products Regulatory Agency) was the first stringent regulatory authority to issue an emergency use authorization for the Pfizer vaccine, and that was 326 days after the release of the viral genetic sequences that demonstrated that we were dealing with a new coronavirus.
That, in itself, was remarkable given that the shortest vaccine development timeline from isolation of a virus to licensure of a vaccine previously was four years and nine months, back in the 1960s with the mumps vaccine.
We think that the speed of trials can be increased if future efforts take advantage of the best-in-class approaches, such as adaptive trials, that were tried and accepted in 2020, reducing development timelines by at least another two to three months.
And then if we make investments in the infrastructure for testing vaccines, and work with regulators to develop new concepts of how to regulate emergency products, we think we can get much closer to the 100-day target.
If we face a truly catastrophic threat in the future – something much worse than COVID-19, we think the 100-day goal is what we need to be able to achieve if we are to have any hope of preventing a global catastrophe. It’s not good enough to say ‘we can’t do it.’
HOW DO ADAPTIVE TRIALS SPEED UP DEVELOPMENT?
Pfizer and BioNTech, who started their first-in-human clinical trial five and a half weeks after Moderna, actually gained two months on Moderna by using a really innovative adaptive clinical trial design.
What Pfizer and BioNTech did was lots of things in parallel, that tested different doses and two different vaccine constructs. And then they honed down and rolled immediately from the Phase One, directly into Phase Two.
So, all of these aspects were combined into a single study.
Another thing they did, that was really important, was incredibly rapid enrolment of volunteers for their Phase Three across more than 150 sites worldwide.
But if you had pre-existing cohorts, that is people who have signed up for trials already, you could shorten this phase as well.
So, if you just combined the Moderna speed to clinic and the Pfizer and BioNTech speed from first in human test to being licensed, you’ve already shortened your timelines by close to two months.
When it comes to coronavirus, there’s an immense amount of prior, vaccinology and immunology, that has now created the foundation both for the rapid response platforms and for these new approaches to vaccine development.
We are standing now on the shoulders of giants.
HOW LONG WILL IT TAKE TO DELIVER YOUR 100 DAY TARGET?
The $3.5 billion dollars is the CEPI contribution to what has to be a global project, one that needs to be embraced and indeed has been embraced by the G7 and G20, the world’s seven leading advanced economies and 20 major economic and political powers, respectively.
Having that buy-in at the senior political and scientific level, we now need to engage the respective national scientific institutions within the G7 and G20.
We have a lot of work to do assuming that there is a collective global effort around the core idea of working with the prototype pathogens and working to compress vaccine development timelines.
But I would say that it’s plausible, because we have the technology already and we essentially know what we need to do. With a concerted global effort, I believe we can very substantially reduce future pandemic risk within five to 10 years.
My team loves to refer to what we’re doing as our moon-shot, since our ambition is on the time scale of and of an ambition comparable to the Apollo programme.
When that programme was announced, the problems that needed to be solved to achieve NASA’s goal were fairly well-defined and what was needed was focus, resources, engineering, and political will.
And that’s what we need to be much better prepared for pandemics.
HOW CAN WE MAKE THE DISTRIBUTION OF VACCINES FAIR?
A quest for equitable and accelerated vaccine distribution led to the creation of the COVAX facility, a joint effort of CEPI, GAVI, the Vaccine Alliance and the World Health Organization, joined by UNICEF.
CEPI has played a central role in the global response to COVID-19, creating the world’s largest portfolio of COVID-19 vaccines and aspiring to make two billion doses accessible to the 190+ economies participating in COVAX.
But COVAX has faced challenges. While high and upper-middle-income nations have seen almost 75% of eligible people get at least one shot of COVID-19 vaccine, only 41% have in lower-middle-income and 5% have in low-income countries.
The fundamental problem that generated the inequity that we’ve seen was the initial scarcity of COVID19 vaccine. When there’s scarcity, there will be inequity, because the haves will take, and the have-nots will be left out.
There are two sources of that scarcity. The first is that currently global manufacturing capacity (this a little bit of an oversimplification, but not much) is basically concentrated in the US, the UK and Europe, China, and India.
Those regions have vast populations that have to be served. And the rest of the world is out in the cold until those regions take care of themselves.
So, you’ve got to have more manufacturing capacity. And it’s not just any manufacturing capacity — you have got to have more globally distributed manufacturing capacity. And you’ve got to have the rapid response platforms globally distributed.
If we can do that, you attack the inequity problem from a couple of dimensions, one, you shorten the period of global scarcity.
Secondly, you also make sure that regions have some degree of self-sufficiency and are not wholly dependent on offshore sourcing of vaccines.
So that’s a big problem, but the solution is pretty obvious. It’s a question of are we going to put the resources in, and do we have the political will to do this? And can we come up with sustainable business models?
To conclude, we now have the tools to dramatically reduce or eliminate the risk of future epidemics and pandemics.
HOW CAN I FIND OUT MORE?
There is more information in my earlier blog posts (including some in German by focusTerra, ETH Zürich, with additional information on Switzerland), from the UK Research and Innovation, UKRI, the EU, US Centers for Disease Control, WHO, on this COVID-19 portal and Our World in Data.