Lessons Learned from Ebola Virus Vaccine Trials
At the National Foundation for Infectious Diseases Annual Conference on Vaccine Research, presenters drew pointed comparisons between the 2014-15 Ebola epidemic and the current Zika virus disease epidemic. A session on multi-sector global efforts to test an Ebola virus disease vaccine (EVD) brought together representatives from the US Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO), the Norwegian Institute of Public Health, and Gavi.
Anne Schuchat, MD, Principal Deputy Director of the CDC, prefaced her talk by noting that the West African EVD epidemic was the largest outbreak CDC has responded to and involved ten times as many cases as all previously known EVD outbreaks combined. So, she says, we learned a great deal about the disease that we hadn’t known before, such as the persistence of Ebola virus in body fluids long after initial infection.
Soon after the WHO announced that the Ebola outbreak was an international public health emergency in June 2014, talks began at WHO, CDC, and in other organizations about the possibility of deploying EVD vaccines. However, although good preclinical (that is, non-human) data existed on the safety and efficacy of two vaccine candidates, Phase 1 trials, which assess vaccine safety in humans, had not yet been attempted. Vasee Moorthy, MD, PhD, who works in vaccine development at the WHO, noted in his talk that some groups advocated deploying an EVD vaccine as widely as possible in outbreak areas, without performing clinical trials at all. However, within a month of the WHO emergency announcement, Phase 1 trials of two EVD vaccine candidates had begun in high-income countries and proceeded quickly, as did the subsequent Phase 2/Phase 3 trials in Africa.
Schuchat outlined the risk groups for EVD, whom the clinical trials enrolled. This are people who had close contact with the ill: healthcare workers, family members, sanitation and burial workers, and funeral attendees. (Children, who are often in high risk groups for infection, were not at particularly high risk for acquisition in this epidemic because they were not so involved in patient care.) More than 8,000 people were enrolled in the vaccine trial in Sierra Leone, and another trial was conducted in Guinea. The WHO presents a list of the trials and results that have been published to date here. In short, the results have been encouraging, with lower disease incidence in vaccinated groups and only mild to moderate short-term side effects seen in those who received vaccine.
The specter of the current Zika virus disease outbreak was not far from anyone’s mind, including the presenters. Moorthy noted that the WHO had hoped to capitalize on the lessons learned from engaging research and development sectors for the EVD vaccine trials so that they would have a blueprint in place for the next outbreak. The Zika virus disease epidemic in the Western Hemisphere, however, came a bit too early, as the WHO’s blueprint is not yet ready.
Jon Pearmen, MS, of Gavi, observed that the Ebola crisis showed the failure of the vaccine market in developing a vaccine that has no established commercial market. Data necessary to launch Phase 1 EVD vaccine trials in humans had been available since 2005, and yet no entity moved the vaccine forward until the 2014 crisis occurred.
Gavi has many questions about their role in supporting vaccines for use in outbreaks and for emerging diseases. This kind of support is very different from their main role, which is to support vaccines that are part of countries’ recommended childhood and adolescent immunization platforms. To what extent should Gavi take a more deliberate approach to support developing countries in preventing, detecting, and responding to outbreaks? Though these questions haven’t been answered, Gavi has provided $5 million to support development of Merck’s live attenuated EVD vaccine. And in return, Merck has pledged that 300,000 doses of their EVD vaccine will be available from May 2016 for use in expanded clinical trials and/or outbreak emergencies and that they will pursue licensure of the vaccine.
One of the main lessons from the EVD experience unfortunately doesn’t apply to Zika: for Ebola, having already conducted phase 1 vaccine trials in humans would have greatly speeded the deployment of vaccine for outbreak control. But we’re much farther from being ready for phase 1 trials for Zika, as the preclinical data haven’t yet been generated due to the immaturity of vaccine research.
The conference will present a talk on Zika virus vaccine development on Tuesday, April 17. And on May 16, here at The College of Physicians of Philadelphia, we are hosting a Zika talk by prominent researcher Scott Weaver, PhD. You can register for the talk here.