Last week marked the first time since the beginning of the Ebola epidemic in West Africa when all three of the worst-hit countries had gone 42 days without a single new case. If there is such a thing as an official end to this nightmare, we had hoped that this was it. Yet the next day, another case was reported in Sierra Leone. So with more than 11,000 people dead, and a further 28,500 infected with continued spread, the question now is, are we today in a better position than two years ago to prevent such a tragedy from happening again?
Given the promising interim results from last year’s phase 3 vaccine trials, at first glance it would appear that there are certainly grounds for optimism. The efficacy data showed that we now have a vaccine that is extremely effective at preventing the further spread of the virus, so effective in fact that the ring vaccination trials were prematurely halted in order to make the vaccine available to delayed control cohorts. So, to prevent future epidemics surely all we need to do now is create a vaccine stockpile, right?
Unfortunately, it is not as straightforward as that. The fact is rare diseases with epidemic potential pose a uniquely challenging set of problems. This is one reason why we were unable to prevent an isolated outbreak from turning into an epidemic in the first place. This was partly due to the virus finding a way to spread to urban populations. But also because the sporadic nature of Ebola meant that there was no market potential to stimulate the development of a licensed vaccine – with only a couple of dozen cases every few years in a typical outbreak, usually in very impoverished, rural African communities, who would pay for it?
Even now when we have a promising vaccine candidate with efficacy data and a handful of other promising vaccines with clinical and animal data, there is still no guarantee that these will be developed into fully licensed products. Adding to the challenge is the fact that with Ebola the set of conditions needed in order to carry out clinical trials of sufficient scale, are precisely the conditions we wish to avoid, namely another epidemic. Although necessity might suggest that we rush the vaccine into wide-scale use, this needs to be carefully considered. After all global health organisations should not be in the business of purchasing and distributing unlicensed vaccines. So then, what path should be used to turn one or more of these into a licensed product that can be stockpiled for use in future outbreaks?
Even with the epidemic waning, it is clear that this is not the last we have seen of Ebola, so how do we also ensure that development of this vaccine, Merck’s rVSV-ZEBOV, and any other promising candidates, do not once again stall? Remember, these antigens were originally developed more than a decade ago, but were then shelved because there was no perceived market. The only reason rVSV-ZEBOV made it to phase 3 trials at all is because the cost was shared between Merck, donor governments and research foundations, and even that was only months after the outbreak got out of control.
So what exactly has changed to incentivise manufacturers to run the regulatory gauntlet and invest in the costly process of getting their vaccine licensed? Moreover, given that we are unlikely to see this process completed and have a licensed product any sooner than 2018, how do we ensure that this, or any other suitable vaccine, is available and in sufficient quantities should the need the arises before then?
In global health terms, these are extraordinary circumstances, but even so that doesn’t mean we should start making exceptions or bend the rules. Instead we have to be steadfast and think inside the box, that is find solutions which fall within existing regulations. This is critically important, not just to avoid creating dangerous precedents, but also because as we charter new ground we need to establish a regulatory framework as we go, whether it’s for Ebola vaccines or the future development of those designed to protect against other neglected yet extremely virulent pathogens.
Indeed, this sort of approach has already been used to help us end this epidemic. In the absence of a licensed Ebola vaccine, we were able to use phase 3 clinical trials, to help contribute to the prevention of the spread of the virus and ultimately bring it under control. And now, we are doing something equally innovative to prepare for, and hopefully prevent, the next epidemic. As part of an advanced purchase commitment (APC) my organisation, Gavi, the Vaccine Alliance, has provided Merck with a prepayment of US$ 5 million against future doses of licensed rVSV-ZEBOV. In return Merck has given assurances that it will continue to pursue full licensure of the vaccine and ensure availability of 300,000 doses, which could be deployed rapidly, for example, under a Emergency Use Assessment and Listing (EUAL).
Doses could only be used under a very narrow set of circumstances. But for now what it means is that if we do have another flare up, or a fresh outbreak, the global health community will at least be in a position to deploy experimental doses immediately and so for the first time have a weapon to help halt the spread of the virus. It means we are now better prepared.
What it doesn’t mean though is that we’ve solved all our problems. For example, while rVSV-ZEBOV has proved highly effective at stopping the spread of Ebola during epidemics, we don’t know if it is the best candidate for the long-term prophylactic protection of healthcare workers. Even so, at least we have a further element that can help incentivise manufacturers to take their experimental vaccines all the way, and have an emergency reserve supply of experimental doses if we need them. And not just for Ebola. Potentially this kind of APC could be a basis potentially for vaccines protecting against other diseases.