ERVEBO: The inside story of the Ebola Vaccine


BtoBio Innovation


Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation




ERVEBO: The inside story of the Ebola Vaccine




In Special Report #40 of November 13, 2019, we had reported about the approval by the European Commission of Ervebo, the world first Ebola vaccine and quoting Merck CEO Ken Frazier saying” this approval is a historic milestone and a testament to the power of science, innovation and public-private partnership”  We now wish to briefly report about the inside story of how scientists across three continents worked together to make this vaccine available, referring to a comprehensive publication by Helen Branswell, a senior writer at STAT.


In the spring of 2014, when Ebola exploded across West Africa taking finally as many as 28 000 lives, a scientist named Gary Kobinger who had succeed to Dr. Heinz Feldman at Canada’s National Microbiology Laboratory in Winnipeg was already intensively working on an Ebola vaccine His vaccine was quite effective in animal models and had even been produced as a human-grade vaccine, but at the time, no biopharmaceutical company showed any interest and even the World Health Organisation (WHO) had declined the offer to testing it in people. With sporadic outbreaks of Ebola there was no opportunity to consider a rigorous clinical experimental trial.  “That big outbreak in 2014, was a game-changer and reminded people that this exotic virus could become a real public threat regionally as well as in a global perspective” said Dr. Heinz Feldman who had initiated the work on the vaccine now known as rVSV-ZEBOV.


The story begins in 1990, at Yale University where John Rose was trying to figure out a way to use a livestock virus called vesicular stomatitis virus, or VSV, as a vaccine delivery system. VSV can infect people but does not sicken them because the human immune system response to the virus is rapid and produces a very high level of antibodies. For years Rose’s team was manipulating the VSV to add in genes of other viruses without success. In 1994, Rose was informed that a team in Marburg (Germany) had been successful when using a rabies virus, thus opening up a new area of research for the development of experimental vaccines for bird flu, measles, SARS, Zika and other pathogens. Ebola had not been tested because at the time it was considered as the most dangerous virus. The work by Rose was patented by Yale and licensed to Wyeth Pharmaceuticals and later on Rose shared his VSV vector with as many as 100 laboratories worldwide including the already mentioned laboratory in Marburg, a place which had made the headlines, in 1967, with the outbreak of the later named Marburg virus (caught from imported primates used for research purposes). In 1980, at the Philipps-University Marburg there was no research performed either on Marburg or Ebola viruses. Heinz Feldman a young student at the Institute of Virology, led by Hans-Dieter Klenk, started studying the impact of introducing Ebola genes into VSV with great success but could not perform animal studies because of the lack of high-containment laboratories.


At more or less the same time, Canada was building a new national microbiology laboratory that included biosafety level 4 facilities which are requested to study Ebola. When Feldman was recruited there to lead the special pathogen team, he was authorized to take the Ebola VSV construct with him in order to continue his work which then became the “Canadian Vaccine”. At the time Feldman was not working on vaccines “We used the construct as a model to study the glycoprotein, which according to Gary Nabel, then head of the National Institutes of Health’s Vaccine Research Center, was the cause of the damage when Ebola infects people. The hypothesis was wrong and when animals were exposed to the VSV virus containing the Ebola glycoprotein, they all survived. These observations were the real starting point of the Ebola vaccine programme. In 2003, the programme could have been definitively stopped because of the outbreak of SARS in Hong Kong which had spread to Toronto. Feldman’s team work on Ebola was put on hold and fortunately resumed a few months later with an experiment performed in monkeys at Geisbert’s laboratory, an Ebola expert at the US Army Medical Institute of Infectious Diseases, with great success. The study was published in Nature Medicine, in 2005, making clear to the entire scientific community that the modified VSV vector loaded with Ebola glycoprotein was safe and could become the foundation of an effective human vaccine. Although very exciting, nobody was keen to develop a human vaccine for a virus that had killed about 1,300 people over 30 years in poor countries. In 2008 Feldman left Winnipeg to become head of the virology programme at the NIH’s Rocky Mountain Laboratory in Hamilton in Montana.


In March 2009 a German researcher pierced her finger with a needle containing the Ebola virus. The University Medical Center Hamburg, where she was taken, reached out to the US and Canada seeking for help. She was offered the VSV vaccine although the vaccine was not human-grade. She developed strong fever with no way to know if it was a response of her immune system or from the Ebola infection. She survived and it was impossible to know if the vaccine had been effective or if she had not been infected in the first place.


Once the patent was secured and with the permission of Wyeth to use the platform to produce Ebola and other haemorrhagic fewer vaccines, the Winnipeg laboratory was seeking for a development partner which it found with BioProtection Systems, a spinoff of NewLink Genetics , a company working on cancer vaccines. The company had no interest in Ebola or in infectious disease vaccines and had made the licensing acquisition to enhance its portfolio and get more funding.  NewLink acquired the exclusive rights from the Canadian government for $156 000 for each product it would develop with attached royalties. The company was later acquired by Lumos Pharma and kept it as a scientific concept, until the West African Ebola outbreak in 2014.


On March 23, 2014, the WHO reported a “rapidly” evolving situation in Guinea with 49 cases and 29 deaths. The following day the numbers were 86 cases and 59 deaths. By the end of March, Liberia, one of Guinea’s neighbours, was claiming possible cases. Kobinger from Canada and GSK, who was developing its own vaccine, offered their support to WHO  who turned it down. Ebola was spreading from Guinea, to Liberia and Sierra Leone, and Médecins sans Frontières (MSF), a French based non-profit health organisation had been warning WHO that the conditions on the ground were rapidly worsening and pushing for using the VSV vaccine. On August 8, 2014 the WHO declared the outbreak of a global health emergency and the Canadian government announced it was donating the vaccine to the agency. At this very moment, nothing was known about the safety and the efficacy of the vaccine in humans and how one could conduct a controlled clinical trial in the midst of an epidemic. Conducting clinical trials with untested drugs or vaccines in Africa is unethical, because clinical safeguards are often missing. Nevertheless, the WHO concluded that it was “ethical imperative” to try experimental vaccines or other therapies given the extraordinary threat Ebola represented. At the same time WHO has decided that in order to use the Canadian VSV vaccine, clinical trials first had to assess its safety and establish the most appropriate dose in various countries (USA, Canada, Germany, Switzerland, Gabon and Kenya). NewLink did not have the expertise to run such a study, in fact the company had never conducted any clinical trial. The WHO was looking for a more experienced pharmaceutical company who could partner with NewLink: Sanofi Pasteur, GSK, J&J, Novartis all turned down the offer, either by lack of interest or because they were developing their own vaccines. Merck, who had experience in producing vaccines in the types of cells VSV was made in, took the risk to move forward. Dr. Julie Gerberding, Merck’s executive vice president and chief patient officer said there was ”moral clarity” at Merck that this was something the company should do. In the autumn of 2014 negotiations between Merck and NewLink to licence the vaccine were ongoing and the deal was announced on November 24, 2014 whereby Merck was paying NewLink $50 million for the licence of the VSV vaccine.


The NIH had reached an agreement with Liberia to test both the VSV and the GSK vaccines. The Center for Disease Control and Prevention (CDC) was to test the vaccines in Sierra Leone. Guinea had also proposed to participate in the trial but, due to the weakness of the country’s healthcare infrastructure, made it too challenging at first hand although an independent study was launched there too. The WHO with the support of MSF would conduct an independent trial in Guinea. The clinical plan was to use an approach called ring vaccination. People who had been in direct contact with anyone infected with Ebola would be vaccinated in order to block the virus from spreading. The rings were randomly assigned with immediate vaccination in a kind of adaptive trial design. Guinea health professionals made up the bulk of the team that conducted the ring vaccination. On July 31, 2015, the findings of the trial were published in The Lancet. In less than 12 months, 12 clinical trials running from “first in man” dosing to a phase 3 trial had been conducted.  The Lancet editorial called the trial “a remarkable scientific and logistical achievement”. Results were far of being clear cut. The Guinea vaccine trial was the only one conclusive. The trials in Sierra Leone and Liberia had not enrolled enough patients to reach a conclusion. The study triggered heated debates over whether adaptive design studies were sufficient to prove VSV was effective. Both the findings and the approach were criticized and to this day still challenged by some experts. Detractors became vocals. “It was ugly”….  “This is not a study, only a randomised controlled trial”. In 2017, the US National Academy of Sciences issued a report on how to conduct trials during disease outbreaks that was highly critical about the way the Ebola trial had been conducted and moreover over its findings. The vaccine had been found effective but the number of people enrolled was limited. The results were nevertheless convincing enough for Merck to move forward with the vaccine now named rVSV-ZEBOV and with the support of Biomedical Advanced Research and Development Authority (BARDA), who invested $176 million to support Merck’s manufacturing and validation of its Burgwedel manufacturing site in Germany.


When Ebola broke out again in the Democratic Republic of Congo in the spring of 2018, the country agreed to use the rVSV6ZEBOV vaccine under a “compassionate use” protocol within eight days after the outbreak was declared.  Since then, 260 000 people have been vaccinated.


On November 11, 2019, Ervebo or rVSV-ZEBOV was approved by the European Commission for the first time by any regulatory agency. On December 21, the US FDA also approved the vaccine.




January 9, 2020




This document has been prepared by btobioinnovation and is provided to you for information purposes only.  The information contained in this document has been obtained from sources that btobioinnovation believes are reliable but btobioinnovation does not warrant that it is accurate or complete. The views presented in this document are those of btobioinnovation’s editor at the time of writing and are subject to change.  btobioinnovation has no obligation to update its opinions or the information in this document.



Share :