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The End of Ebola: Inside the Race to Finish Vaccine Trials in Liberia

VICE News met patients, doctors, and public health officials in Monrovia as they worked to develop a vaccine that could prevent the next deadly Ebola outbreak.

by Kayla Ruble
Apr 19 2015, 6:30pm

Photo by Kayla Ruble/VICE News

It's barely 8am in Monrovia but the air is already thick. Motorbikes roar through the crowded streets of the Liberian capital's New Kru Town neighborhood. Dozens of men and women sit along rows of wooden benches in an open-air section at the back of the public Redemption Hospital. Jacob Choko is stationed in the front row, holding a color-coded plastic card and waiting patiently for his number to be called.

Choko walked to the hospital on the morning of March 5 from his home nearby, leaving his wife to care for their newborn baby and three-year-old daughter. When it's his turn, Choko, who wears jeans and a soccer jersey, is ushered to a seat at a plastic card table across from a healthcare worker whose face is concealed behind a protective mask. Pen in hand, she takes down his personal information and asks a series of questions.

"Have you ever had vomiting?"

"Has anyone in your family died recently?"

"Have you ever had Ebola?"

Last July, Redemption Hospital saw the Ebola virus spread from an unsuspecting patient to its doctors and out into the community. At the time, the devastating potential of the deadly hemorrhagic fever was only vaguely understood. But nine months and more than 10,000 infections later in Liberia alone, the deadliest Ebola outbreak in history is on the verge of burning out in the country. Redemption is now the site of vaccine trials that, if successful, could could be an essential tool for fighting future outbreaks.

Despite the semi-regular occurrence of small outbreaks, other than supportive care like IV fluids, no medical treatments or vaccines have been successfully developed and brought to market for Ebola, which in some instances has carried mortality rates upward of 80 percent.

Choko admits to having had a "runny stomach" not long ago, but answers "no" to all of the other questions. Satisfied that he doesn't have the deadly hemorrhagic fever, the masked nurse allows Choko to proceed to the next station to meet with counselling teams and doctors. He will ultimately decide to receive an experimental vaccine that, at the time, had been tested on fewer than 500 local volunteers.

"The first people in our community to participate, up until this time are still strong," Choko told VICE News, saying the experiences of his friends and neighbors encouraged him to participate. "I saw their appearance, nothing happened to them, so it encouraged me to come too."

The trial started in early February, with Choko and the other participants receiving either one of two vaccines or a placebo. A partnership between the Liberian government, the US National Institute for Allergy and Infectious Disease (NIAID), and PREVAIL, an acronym for the Partnership for Research and Ebola Vaccines in Liberia, brought the trial vaccine candidates to Monrovia. While the program also focuses on building infrastructure for research and post-Ebola treatment, the trials have been its highest-profile endeavor.

On the opposite side of the city from Redemption, in a neighborhood populated with embassies and roads filled with NGO vehicles, Dr. Stephen Kennedy sits behind a deep wooden desk covered with file folders and stacks of papers. On the wall to the right is a white board dictating his schedule for the week, filled with meetings and even a visit to Redemption to check on the trial's progress. After the Ebola crisis hit Liberia last spring, the government appointed the Liberian-born, American-trained doctor the country's Ebola research coordinator. Now, nearly a year later, he sits at the head of the Liberian side of PREVAIL.

"A lot of people [were] dying, personal friends, colleagues, people from the community where I live and grew up, where you can hardly provide any support or medical assistance," he told VICE News in March, detailing why he was compelled to accept the government's request. "I can be a part of that to ensure that we no longer experience such devastation."

By the looks of his upcoming schedule, it wouldn't be a stretch to assume most of the paperwork piled on his desk consists of Ebola-related research, and that somewhere in that stack lies data related to the two candidates for vaccines he helped bring to Monrovia. The first is the cAd3 vaccine, developed by GlaxoSmithKline and funded by the US government, it is made up of the shell of a chimpanzee cold virus and a single Ebola protein from the Zaire strain of the virus. The second is the VSV vaccine, which was patented by the Public Health Agency of Canada and based on the vesicular stomatitis virus. The VSV vaccine aims to immunize against three types of Ebola and the Marburg virus, which also causes hemorrhagic fevers.

Kennedy rolled up his sleeves to receive an injection on the first day of the trial at Redemption Hospital in February and became an active participant in the groundbreaking trials. But this moment came after months of working with global experts, sifting through research, and working to develop the partnership with NIAID. Kennedy poured over data and information to ensure that his team was involved in the decision-making and had agency over how the trials would run in his home country.

"This thing didn't just come from nowhere and drop February 1, it's been a long-going process," he told VICE News.

It would be misleading to think the efforts of the rush to develop an Ebola vaccine began with the onset of the 2014 outbreak. That story starts not only months before the February trials got underway, but years before the deadly hemorrhagic fever wreaked havoc in West Africa.

***

In September 1976, the first-ever Ebola outbreak occurred in the country of Zaire, now the Democratic Republic of Congo (DRC). The mysterious and then unnamed virus made its debut in rural forest villages in the country, eventually spreading to a hospital staffed by Belgian nuns — infecting 318 people and killing 280 in total.

A consortium of researchers and health experts worked to stem the outbreak and ultimately identified the virus, naming it after the Ebola River in northern DRC, with the species identified as the Zaire strain. In the nearly four decades since, different strains of the Ebola virus have appeared in Africa 26 separate times, with a recent large spread occurring in Uganda in 2000 with 425 people infected.

But none of the drugs in development had made it to the clinical trial phase by the time the Ebola virus took hold in Guinea, where it is believed to have made the essential jump from an animal host to a human vector in December 2013 in the prefecture of Gueckedou — potentially traveling from a bat to a 2-year-old boy. Ultimately, the virus made it across the border to Liberia and Sierra Leone in spring 2014.

"These are the kinds of diseases, and there are many of them, described as neglected tropical diseases, that don't lend themselves to make them enticing candidates for manufacturing," Jason Schwartz, a bioethics fellow at Princeton University, told VICE News. "This is not a new story."

What is new, however, is the fact that such a devastating outbreak was the result of a disease we've known about for nearly four decades. While being a so-called "neglected" tropical disease likely kept Ebola from becoming a priority in the pharmaceutical world, that doesn't mean research wasn't ongoing or that no one was pursuing treatment and vaccine development.

"I don't want to say it's unprecedented, but it's rare," Schwartz explained, "[to have] a re-emerging threat with late stage but active research progress that could ramp into high gear."

Between the first Ebola outbreak in 1976 and the deadliest in 2014, multiple drugs and vaccines were at various stages of development, largely thanks to investment and funding from governments like the US — often with issues of national security in mind. One of those drugs sitting on a shelf was GSK's cAd3-ZEBOV vaccine, which has finally made its way to Monrovia. Clinical development for the vaccine began in 2011, and the first step of clinical trials in humans was scheduled for early 2015. Similarly, researchers with the Public Health Agency of Canada's National Microbiology Laboratory developed the VSV vaccine, which was first tried in monkeys between 2000 and 2005.

Throughout the outbreak, World Health Organization (WHO) officials repeatedly blamed the profit-driven pharmaceutical industry for the fact that a drug had never been approved. After an August meeting discussing the ethics of speeding up Ebola drug development, WHO's assistant director-general for health systems Marie-Paule Kieny highlighted ways in which the pharmaceutical market had hindered progress for Ebola drugs.

'The fact that there is currently no registered drug for Ebola is a market failure.'

"We must also recognize that the fact that there is currently no registered drug for Ebola is a market failure," she said. "It's a market failure because this is typically a disease of poor people in poor countries where there is no market."

When the outbreak peaked in August, however, the narrative began to change as the WHO took steps to evaluate putting unapproved treatments and vaccines on the fast track and make their development a priority.

"The large number of people affected by the 2014 West Africa outbreak, and the high case-fatality rate, have prompted calls to use investigational medical interventions to try to save the lives of patients and to curb the epidemic," the United Nations health agency said in an August 11 statement after hosting its first emergency session on the ethics of the process. In a WHO meeting at the end of September, international experts and stakeholders evaluated efforts to safely and quickly develop a vaccine.

At this point, the Liberian government had already kicked into full gear in the search for medical interventions, including seeking help from the US government for anything that could minimize the epidemic's damage, whether that pertained to vaccines, treatments, or standard care.

"We were open to anything that could help us minimize the threat of the epidemic crisis," Kennedy explained.

These efforts led to PREVAIL — the partnership between the Liberian government and NIAID —  and, ultimately, the arrival of the vaccine trials in Monrovia, with Kennedy and NIAID's Dr. Clifford Lane in charge. As Kennedy explained, Liberian doctors and scientists began to review all of the data, determining that the two most promising vaccines in the pipeline were the cAd3 and VSV vaccines.

The first phase of human trials was conducted in Maryland at the end of 2014, having already gone through animal trials. Half of the volunteers received the same injection, but at a low dose, the others at a higher dose. All experienced a sign of immune response to the vaccine — meaning their body generated anti-Ebola antibodies.

When searching for the right vaccine, scientists want to see the body produce anti-Ebola antibodies near the level found in the blood of Ebola survivors, who are immune to the virus once they recover. Testing the blood of trial volunteers can give researchers insight into whether the antibodies are being built up, and in this instance it was clear higher doses of the vaccine produced a better immune response.

Phase two of the human trials were conducted Monrovia, where 600 volunteers went through the process throughout February and March. The aim of this step of the now completed vaccine trial process was to prove the product's safety. In phase two, volunteers are tracked to monitor any health complications or symptoms that may arise. An independent data safety monitoring board evaluates all of the information collected and makes determinations independent of Kennedy and Lane's teams.

"In phase two we do more monitoring of [volunteers] to be able to pick up on safety issues," Lane told VICE News. Volunteers go back to Redemption at various stages for monitoring. Based on data thus far, Lane said there were no concerns to prevent bringing the trial to a larger cohort. These sentiments were validated in a March paper from the trials saying data indicated the vaccine was safe to proceed to a larger phase three, which could include nearly 30,000 patients.

***

When asked whether they will receive the vaccine, it's not uncommon for both health professionals and average Liberian citizens to wince and respond with a shake of the head or a flat-out "no." Public perception has been one of the major obstacles during the trial process.

Despite awareness campaigns throughout Liberia, the spread of inaccurate information was clearly a problem. Reports of mothers not taking their children to get non-Ebola vaccines for fear they will be injected with the Ebola vaccine began to surface after the trials kicked off. Even a medical dean at the country's leading medical schools at the University of Liberia expressed concern.

"The president of this country, the legislature, and the judiciary have no right to allow clinical trial vaccines to be conducted without hearings that involve those who studied medicine in this country," Vuyu Kanda Golakai, dean of the A.M. Dogliotti College of Medicine at the University of Liberia, said during a forum in February.

Kennedy stressed the priority he and the government placed on ensuring their team was equally involved in bringing the vaccine to their country, as with every step of the process.

That independence, whether it means not accepting money from drug companies, or pushing for Liberia to build up its own infectious disease capabilities, is integral for Kennedy. While international experts and stakeholders, government officials, and locals alike, lament both the slow international response to the crisis and the lack of prior efforts to develop Ebola vaccines and treatments, you won't hear that from Kennedy. The American-trained doctor doesn't dwell on the past, but instead has his sights trained on the future, particularly in pursuit of Liberian ownership of the successes, the problems, and the lessons learned from the country's first-ever Ebola outbreak.

When asked about the lack of investment in a disease like Ebola, largely seen as a developing-country virus, Kennedy sees that as predictable.

'Before this outbreak, the largest was 300 to 400 deaths, so why do you expect pharmaceutical companies to spend billions of dollars for that?'

"Before this outbreak, the largest was 300 to 400 deaths, so why do you expect pharmaceutical companies to spend billions of dollars for that?" Kennedy asked, noting that it was the scale of this epidemic that jumpstarted efforts. "I think it took a different dimension with the unprecedented outbreak, with the huge proportion, three countries affected simultaneously, three large urban cities affected simultaneously, that's unprecedented, never happened in the history of the world before."

The international community face criticism for its slow response to both the outbreak and for pushing vaccines, but to Kennedy that's just a sign Liberians need to build up their capacity.

"If you look at the SARS epidemic in Asia, the response was a little bit different. There was a Marshall plan to address that, you don't see that here. We can't continue to dwell on that," he said.

"The lesson learned is that the nationals of these countries, the nationals of the sub-region should begin to step out, to prepare institutions, prepare infrastructure, to begin to address infectious diseases," he explained. "If you do that, you don't have to wait for international response."

With the focus on public health and partnerships like PREVAIL, Kennedy is dedicated to building up capacity in the country and the region. Efforts are currently underway to expand Liberia's biomedical research by creating labs at the highest biosafety levels. Another important step is ensuring that various testing capabilities exist, so that the governments don't have to wait on US equipment. Kennedy said he hopes the epidemic's devastating effects will push more Liberians into fields of Ebola research — similar to what has happened in the DRC four decades after the first outbreak. The country even sent a team of medical experts to assist in West Africa. Uganda, where five outbreaks have occurred in the last 15 years, also offered to send doctors and experts to the region. 

"The bottom line is that, Ebola, despite the devastation, it also brought us back to the drawing board to rethink how we can help fix some of the health crisis we face in the West African subregion," Kennedy said.

"Liberia has played a very significant role in trying to curtail this epidemic. So what it has done, it has created a new breed of Liberian professionals. What's going to happen is, there's going to be a migration of Liberian professionals into other international organizations where there is another epidemic," he said, explaining that he hoped to see an influx of young Liberians looking to go into medical and scientific fields as a result of the Ebola outbreak. "If we cannot reinvigorate the scientific space in this country, then I don't know [what] else do we need to do that."

***

Beyond public opinion, the other major obstacle — and the elephant in the room — for all of the vaccine trials that are underway or in some phase of development, is the fact that the Ebola outbreak is no longer out of control like it once was. When talk of vaccines began in August, media coverage showed bodies lying in the streets of Monrovia. Predictions swirled that tens of thousands in West Africa would die if the world didn't ramp up efforts to stamp out Ebola. Debate and research continued through the fall, but by November, the cases in Liberia started to decline drastically. While spikes have occurred in Sierra Leone and Guinea over the last few months, the outbreak appears to be on its way out.

"We're at this different stage of the outbreak," Schwartz, the bioethicist, explained, saying there is now a problem in that having so few cases makes it extremely difficult to clinically test the vaccines in the face of the epidemic, a crucial aspect of proving efficacy. "[It's a] fortunate problem: How will we be sure these vaccines are effective?"

The rush is on for the medical and research community to figure out everything they can while there are still unfolding cases, according to Schwartz.

"So much will really depend on the fact that the epidemic is waning," he said. "How will the research respond? How will the research and policy makers respond? It really will be a huge turning point in this story of the path to the Ebola vaccine."

PREVAIL could continue on its trajectory of vaccinating 27,000 Liberians, the initial number set to prove whether or not the vaccines are effective in phase three of the trial which moves beyond testing for safety and aims to prove efficacy. Since March 1, however, there has only been one new infection in the country, meaning it's highly unlikely any of those volunteers would ever face the risk of infection. Schwartz said this would allow for the researchers to pursue the "gold standard" of trials, as was done in phase two in Monrovia, without the ethical concerns of continuing to include a placebo in areas of continued transmission, say in Guinea and Sierra Leone. Researchers could monitor the anti-Ebola antibodies that are produced to evaluate immune responses through blood samples, and in theory, they would know whether the immune system had responded appropriately.

But this would fail to prove absolute protection. As the NIAID's Dr. Lane explained, for the minimum level of protection from a vaccine trial, including the desired placebo, you want to prove 50 percent efficacy for the vaccine to be considered an important public health tool.

"We're cheering for two things, but they're mutually exclusive. [We] want to test vaccine studies and want the epidemic to go away for us to be able to show one or the other vaccine is 50 percent effective," Lane explained.

After the Liberian-based second phase of the trials concluded in March, researchers deemed VSV and cAd3 safe to administer. Now, because of concerns for proving efficacy amid declining cases, Lane said NIAID is exploring options to bring the vaccine trials to hot zones. He noted that pursuing the 27,000 volunteer goal in Liberia doesn't make sense when you have no new cases. But as they pursue other options, they must get into the other countries before the situation repeats itself.

'There's enormous pressure, if we don't get these implemented quickly we may lose the ability to know they work.'

"Once the cases are gone, you're not going to be able to test the vaccine with a clinical end," Lane said. "There's enormous pressure, if we don't get these implemented quickly we may lose the ability to know they work."

As many have pointed out, the fact that the US continued investing in Ebola research over the last few decades — increasingly as the study of biological warfare came into the picture — helped put researchers and developers in a position where they could answer WHO's call for help at an unprecedented speed. But the time it took to bring the human trials to Monrovia is not acceptable in a global world where diseases can travel via plane, according to Jeremy Farrar, a tropical medicine professor and the director of the UK-based medical research charity Wellcome Trust.

"There has been a remarkable, in fact unprecedented, escalation, which has required international collaboration," he said, speaking of the work since the epidemic began. "You say '12 months and that's never happened before.' I think we think that's acceptable, and in my view that's not acceptable, 12 months is too long."

"Really good diagnostic care, really good treatments, and really good vaccines are a critical part in how to control an epidemic," he added, noting all of these pieces are equally crucial and important. Wellcome Trust helped fund the GSK vaccine with a $4 million grant, while putting $15 million total toward Ebola research.

According to Farrar, with the speed infectious diseases can travel, the international community needs to do what it did in a year of the Ebola epidemic in a few days or weeks. Speaking of such diseases in general, he said this will require that work on diagnostic care and vaccines — which we at least know are safe for the diseases we're aware of — are put in motion, while we work on being able to preempt the diseases we don't know about, whether that's studying animal populations or building up response capabilities.

"The world will face emerging infections [that] won't take months to spread," he said. "We may not have a year or two to do these things, we need to be able to condense into days and weeks what has taken months and years."

Farrar also discussed efforts to build trust in local populations to ensure they'll take a vaccine when needed. This kind of trust, he explained, has been an issue throughout the 2014 epidemic. He also stressed that immune system response can at least be monitored through blood tests.

"The worst thing to do would be to stop these vaccine trials. They must be pursued and must be pushed on," he said, noting that people have been predicting the end of the epidemic for some time, but that unfortunately new cases are still appearing. Even so, stopping current research and development on any potential options could be a serious mishap — especially with the possibility that the virus could show up again in one of these countries.

"Imagine if we stop the vaccine trial and three months from now there's another huge outbreak in Monrovia. You would never live with yourself," he said.

***

Back at Redemption Hospital, Choko and other volunteers from the neighborhood wonder whether the vaccine trials will prevent them from traveling abroad. Choko would like to visit his sister in Trenton, New Jersey. A few comment on the fact that they haven't eaten since the day before, holding their stomachs as they express their hunger.

Like many other Liberians, Choko has had a hard time earning money since the Ebola outbreak. New Kru Town, which surrounds the Redemption Hospital and was a target for the vaccine trials, is a poor neighborhood, and many volunteers in the trial seemed motivated to join by the small stipend promised to participants upon completion.

But Choko, as with other volunteers lined up along the wooden benches, also recognized that he could have a role in preventing the virus from spreading again.

"I was paying attention to everything—news, TV or whatever, I [was] following whole Ebola crisis," he said. "I [was] going through it…. In the street people carrying bodies in the car, I've seen it."

"If there's another outbreak, I will help," he said, explaining his desire to keep his wife and children safe. "I try to protect them."

Follow Kayla Ruble on Twitter: @RubleKB