Via Nature News & Comment, an explainer by Declan Butler, Ewen Callaway, and Erika Check Hayden: How Ebola-vaccine success could reshape clinical-trial policy.Excerpt:
For how long does the vaccine work?
That is unknown. The trial was designed to test whether ring vaccination could snuff out outbreaks, and the several weeks of protection that it is known to provide is enough to do this. “That’s good news for an outbreak situation,” says Adrian Hill, director of the Jenner Institute at the University of Oxford, UK, who is involved in testing a different Ebola vaccine. However, he says, it remains to be seen whether the protection lasts any longer. “Will it work at six months? This trial doesn’t tell us that.”
Longer-term — ideally lifelong — immunity is needed for a vaccine to provide sustained protection to health workers and other high-risk groups during an epidemic, or to mass-vaccinate populations should Ebola become endemic. Other vaccine trials, including the one that Hill is involved in, are testing for longer-term protection. But the fall in the number of Ebola cases — to 20–30 per week over the past few months — means that the trials may struggle to provide clear results.
Could the rVSV-ZEBOV vaccine help to end the epidemic in West Africa?
The vaccine will continue to be used in Guinea as part of the clinical trial. Many researchers hope that it will be used in Liberia and Sierra Leone too, to end the epidemic — although case numbers have plummeted, there is a continued risk of flare-ups as well as of spread to nearby countries. However, some regulatory hurdles need to be cleared first. Deployment in those nations could occur as part of an expanded clinical-trial regime or through emergency authorization by regulators, says Gregory Hartl, a spokesperson for the WHO. The authorities there are now considering whether the available data are sufficient to license the vaccine for use outside a clinical-trial setting, a process that could take weeks to months, according to the WHO.
Is it unusual to do a trial during an outbreak?
Yes. Getting clinical trials approved by regulators usually takes years, as does conducting the gold standard of randomized controlled trials. That means that outbreaks tend to be over before trials can even begin. Clinical trials are also usually done in well-equipped research hospitals, and quality trials have generally been considered impossible to carry out in the often-atrocious field conditions of deadly outbreaks (see Nature 513, 13–14; 2014).
The urgency of tackling Ebola changed all that. In September, the WHO-supported collaboration pulled out all the stops to accelerate testing of treatments and vaccines that had shown promise in animals. It cut through the red tape and came up with trial designs that could quickly provide data at least good enough to inform efforts to control the outbreak. The rVSV-ZEBOV trial is one of several that came about as a result.
Can the fast-track approach be applied to other diseases?
Hill suggests that vaccines could quickly be developed for many other epidemic threats. He recommends that research on vaccines against such pathogens be accelerated so that clinical trials can be done now to test their safety; those that pass muster would be stockpiled, ready for efficacy tests as soon as an outbreak occurs. Pathogens considered priority health threats include Marburg virus, which is in the same family as Ebola, and the viruses that cause Middle East respiratory syndrome (MERS), Lassa fever and chikungunya.
Are lessons likely to be learned from rVSV-ZEBOV’s success?
The hope is that it will provide a model for dealing with future outbreaks. “This is illustrating that it is feasible to develop vaccines much faster than we’ve been doing,” says Hill. And there seems to be support for change at the highest level. Margaret Chan, director-general of the WHO, said on 31 July that the agency is developing a “blueprint” for accelerated development of measures to counteract potential epidemics.
The plan aims to reduce the time from the recognition of an outbreak to availability of countermeasures to four months or less, and would include putting trial designs and regulatory approvals in place in advance of an outbreak. “No one wants to see clinicians, doctors, left empty-handed ever again,” said Chan.