Marburg could soon become the second virus in the past year to have experimental vaccine candidates ready for testing under an emergency use listing. Until this point, no licensed vaccines or treatments are available for Marburg. That was also the case with the Sudan strain of Ebola, which caused an outbreak in Uganda with 164 cases and more than 55 deaths in the last quarter of 2022. In that instance, vaccines were shipped in a record 78 days, but the outbreak was brought under control before they could be tested for efficacy and made available.
Currently, Equatorial Guinea and Tanzania are experiencing their very first Marburg outbreaks, and non-pharmaceutical control measures have so far struggled to contain this deadly hemorrhagic filovirus with a mortality rate of more than 50%. In Equatorial Guinea, Marburg has now spread from rural regions to the heavily populated port city of Bata. With the whole region on high alert, a safe and effective vaccine really couldn’t come soon enough.
But while fast-tracking candidate vaccines represents a positive step forward in the race to stop these outbreaks and to improve global health security, it raises an important question. If vaccine candidates already existed for both of these viruses before the outbreaks began, then why weren’t investigational stockpiles of vaccine ready to go when the first cases were detected?
If vaccines are to be ready for testing, then they need to be filled, finished, and ready to go. That means that if another outbreak doesn’t occur within the normal expiration timeline, these vialed vaccines will need to be destroyed and new ones created. This is clearly one of the challenges of carrying out vaccine trials for disease that are prone to sporadic outbreaks, but the real reason for not having them available is arguably one of our biggest global health security blind spots: There is simply no perceived market for these kinds of vaccines.
Covid-19 has shown that when a pandemic is in full swing, producing billions of doses of pandemic vaccine can be profitable because there is huge demand — something I witnessed firsthand as the CEO of Gavi, the Vaccine Alliance, which provides vaccines for more than half the world’s children and, with COVAX, made 1.95 billion doses of Covid-19 vaccines available to 146 countries.
But when it comes to preventing a small, localized outbreak from escalating into an epidemic or global pandemic in the first place, there are fewer incentives. For manufacturers it’s simply not profitable to run the regulatory gauntlet to develop and produce such small volumes, while governments are reluctant to waste money on vaccines that may ultimately never get used.
Given the increasing threats posed by pandemics, if we can’t get this right for known diseases like Marburg and Sudan Ebola, then what hope do we have for future unknown pandemic threats? Even as the total number of cases of Covid-19 continues to rise, the latest research suggests that in any given year there is a 2% risk of us experiencing another Covid-scale pandemic. When you factor in climate change, population growth, urbanization, and human migration, all of which can make it easier for outbreaks to spread and escalate more rapidly, the risk of pandemics could double in the coming decades.
The good news is that pandemics are not inevitable. In theory, if you have good disease surveillance and emergency stockpiles of vaccines on hand, contact tracing and ring vaccination — if the vaccine is efficacious — should make it possible to prevent escalation. The faster the response, the quicker an outbreak can be contained. Vaccinating even just a few dozen people for each case identified could benefit everyone.
However, in practice there are three main challenges to this. The first is the fact that dozens of doses, or even thousands, do not make a market. This means we cannot rely on market forces alone to get these kinds of vaccines developed through trials and approved, which in itself is the second big challenge. Because although diseases like Marburg and Ebola have pandemic potential, more often than not, they burn themselves out or, thankfully, are brought under control through traditional containment measures, such as quarantine, before any vaccines can be tested. The third challenge is that vialed vaccines have more limited shelf lives than storing them in bulk. So, one needs to be comfortable that if there is not another outbreak within the period of the vaccine expiry, the old vials will need to be destroyed and new ones filled — a seemingly low cost for protection against serious outbreaks.
Overcoming all these challenges will require a coordinated global strategy to produce vaccinations for all nine priority pathogens identified by the World Health Organization as having pandemic potential, a list which includes Disease X, a hypothetical as yet undiscovered pathogen.
This is a solvable problem. After the large outbreak of the most common form of Ebola, Ebola Zaire in West Africa in 2014-2015, Gavi created an advance purchase agreement that not only provided incentives for manufacturers to take the product to licensure, but also assured that there would be investigational doses for use in case there were outbreaks in the interim (which there were). We already have the Coalition for Epidemic Preparedness Innovations focusing on the initial science to ensure we have several candidate vaccines for each pathogen. But we also need to advance those candidates as far forward as possible, not just through the animal model and the early clinical testing stages, but also to ensure we always have vialed and quality-tested vaccines that are ready to be tested in populations as soon as the next outbreak strikes.
For the majority of the Marburg candidate vaccines that existed prior to this outbreak that certainly wasn’t the case, because there was no perceived market. So, we also need to establish publicly subsidized markets, supported by G20 governments, to drive the research and development, and the flexible, small-scale manufacturing that will be required to ensure we can have doses as close to ready as possible and in sufficient quantities when we need them. With viral vector and mRNA vaccines we can even do this for Disease X, because these technologies make it possible to carry out much of the work in advance — the genetic sequence for antigens against the unknown disease can be slotted in at the last minute.
But with all of this, small-scale manufacturing will be key. In fact, in the face of the potential for a growing number of outbreaks, we could see traditional large global emergency stockpiles of vaccines increasingly stretched to their limits. This is precisely what happened in Angola in 2016 during the worst yellow fever outbreak in three decades. Fractional doses of vaccine had to be used to prevent the outbreak spreading from the capital Luanda to Kinshasa, the capital city of the Democratic Republic of the Congo. Both cities had populations of 12 million people, yet at the time the global stockpile was 6 million doses.
So, as we look to the future, the strategic use of relatively small vaccine stockpiles to stamp out outbreaks quickly is likely to become increasingly important. Here I’m talking about stockpiles of perhaps tens to hundreds of thousands of doses, instead of millions or billions. Because frankly, if we reach the point where we need billions, then in effect we have already failed.
Seth Berkley is CEO of Gavi, the Vaccine Alliance.
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