Answering the Call: Battling Ebola with Experience

When an outbreak of Ebola exploded last August in the West African countries of Guinea, Liberia, and Sierra Leone, US-based physician-researcher Pat Fast received a call out of the blue.

A representative of the World Health Organization (WHO), phoning from the group’s headquarters in Switzerland, said Fast was needed—immediately—to battle a disease that was spreading rapidly. For only the third time in history, the organization had declared what it designated as a “Public Health Emergency of International Concern,” due to fears that Ebola posed a major health threat to Africa and elsewhere. Fast, an expert on managing vaccine clinical trials, jumped at the chance to help coordinate trials of vaccine candidates intended to prevent infection with this highly contagious and often fatal virus.

“When I first started to work on AIDS vaccines, the critical factor for me was: Is this going to be important in world health and can I help make it happen?” said Fast, speaking from her home base as senior technical advisor at the International AIDS Vaccine Initiative (IAVI) in New York City. “So here was another opportunity where I could help do something important in world health.”

IAVI management cleared her to go, giving her full support. Fast arrived in Geneva shortly after, skipping her hotel and heading directly to the WHO’s headquarters. Marie-Paule Kieny, the assistant director-general, Health Systems and Innovation, at WHO had pulled together a small team to oversee Phase I trials. That group was led by Vasee Moorthy, the technical officer for the Malaria Vaccine Section of WHO.

Those, like Fast, arriving in Geneva to give assistance, as well as others heading to aid efforts in Africa, knew that wars and civil strife had stripped the epidemic-riven areas of necessary medical infrastructure. They understood that fear and mistrust of governments meant that many at risk of infection would be reluctant to seek treatment. And, unlike the 21 Ebola outbreaks preceding it, this one was not waning due to medical intervention. The number of people infected with Ebola was doubling each week. WHO epidemiological models that incorporated factors such as speed of transmission and mobility of a population predicted that over a million could die. 
  
“I said, 'Tell me what to do,'” Fast said when she arrived. “We didn’t know what was going to happen with the epidemic. The universal feeling was that we should do whatever it takes to get those vaccines into the affected countries.” 
 
Fast’s job was to coordinate Phase I clinical trials assessing the safety of a vaccine candidate known as replication competent rVSV-ZEBOV (VSV). This candidate, as well as another known as ChAd3-ZEBOV (ChAd), was shown to be safe and effective in animal studies. ChAd was developed by the US National Institute of Allergy and Infectious Diseases (NIAID) and is now owned by pharmaceutical company GlaxoSmithKline. VSV, developed by the Public Health Agency of Canada, and licensed to NewLink Genetics, is now licensed to Merck. Geneva would serve as the base of operations for the team overseeing the Phase I trials of these vaccines.
 
ChAd uses a strain of cold virus called adenovirus that infects chimpanzees to deliver genetic material from a strain of Ebola. The genetically engineered adenovirus is unable to replicate but it taxis the Ebola gene to a person’s cells, which stimulates an immune response against Ebola. The vaccine candidate for which Fast coordinated trials (VSV) uses an attenuated form of the vesicular stomatitis virus, which mainly infects animals such as rodents and cattle as a delivery vehicle to introduce an Ebola gene that in turn, stimulates an immune response against the Ebola virus. The wild type strain of this virus can cause minor illness in humans, but the virus has purposely been weakened to avoid that possibility.

“There was a big sense of urgency,” Fast said. She helped organize budgets, oversee multi-government documentation, coordinate studies, and facilitate communication between the US, African, and European team.

The WHO-led consortium for VSV included expert clinicians and scientists from Switzerland, Germany, Kenya, Gabon and the UK. Trials were also organized in the US and Canada. “The teams were amazingly skillful. Everyone cooperated,” Fast said. She was especially moved by the courage of health workers who remained at the front lines of the epidemic in the affected countries. All risked their lives. Many died and others endured witnessing the death of colleagues, as well as their patients.
 
The Phase I studies of the two vaccine candidates, conducted at multiple sites, including the US, Canada, Gabon, Germany, Kenya, and Tanzania, provided enough safety data by January of this year to support decisions to proceed with efficacy trials in Africa. Both candidates have been shown to be safe and well tolerated. The results from the trials for rVSV-ZEBOV were published in April in the New England Journal of Medicine, with the ChAd results appearing in NEJM last November. Later stage trials are continuing at sites in Guinea, Liberia, and Sierra Leone. 
 
Thanks to heroic efforts by national and international medical teams, the Ebola epidemic has waned. It may not be possible, during this epidemic, to determine the efficacy of these vaccine candidates in preventing Ebola infection. However, the risk of future epidemics remains, and the WHO and regulators are considering how to proceed. Fast concludes that, in the context of an international emergency, it is possible for accelerated, high-quality Phase I trials to be swiftly executed. There is no question that the crisis situation pushed the development of these vaccine candidates. “A sense of international urgency can break down entrenched attitudes of business-as-usual,” she said. “It would be wonderful to apply this sense of urgency to other areas, such as the need for an HIV vaccine.”

- Kitta MacPherson is a writer for VAX and IAVI Report in New York and an award-winning science journalist.