In a frantic race against time, Lausanne and Geneva hospitals played a pivotal role in fighting the epidemic that is ravaging West Africa. Here we tell this extraordinary story, featuring the tropical disease specialist Blaise Genton.
The Ebola virus has vanished from front-page news, but it continues to rage, especially in the Democratic Republic of the Congo. Two vaccines are currently being used on the ground to halt the disease. French-speaking Switzerland has played a major role in developing the vaccines, overcoming the particularly challenging conditions.
It is Tuesday, 3 September 2014. The Ebola outbreak is devastating Guinea, Sierra Leone and Liberia. The World Health Organization (WHO) declared the epidemic a “public health emergency of international concern” nearly seven months after the first cases were detected. Marie-Paule Kieny, at the time Assistant Director-General of the WHO, picked up her phone and called Blaise Genton. Specialised in tropical medicine, the Vaud native is co-chief of the Department of Training Research and Innovation at Unisanté, the Centre for Primary Care and Public Health, in Lausanne.
The WHO expert knows him well, especially from his involvement in fighting malaria in Africa. She asked him if he could lead tests to develop vaccines against the Ebola virus in a very short time frame. The professor contacted his colleague François Spertini, an immunology expert at Lausanne University Hospital (CHUV), to find out if he was prepared to join him in conducting a study over three months, a study that would normally take three years. That was when the race against time began, when the WHO, the CHUV and Geneva University Hospitals (HUG) came together to work in close collaboration.
At the end of 2014, Ebola had already caused the death of more than 2,000 people. “Public opinion was affected by what was happening in West Africa,” Blaise Genton recalls. He and his colleagues swiftly informed the organisations concerned by the development of a vaccine – such as the ethics committee and the regulatory authority Swissmedic – so that they would be ready to face the requests. Everyone did their part.
“We instantly had 500 people queuing up, here in French-speaking Switzerland, willing to volunteer for the tests. That’s totally unusual.”
Six weeks after Marie-Paul Kieny’s call, the first vaccine was injected in Lausanne. “It was an exceptional achievement. Forming a team, developing procedures, finding volunteers, obtaining all the approvals and authorisations – all that usually takes at least two years,” he says, adding that the short distance between Geneva and Lausanne helped them advance more collaboratively and more quickly.
Two vaccines were tested. The first, VSV-ZEBOV, was Canadian. Tested at HUG, the vaccine was developed by the Public Health Agency of Canada and manufactured by the pharmaceutical company Merck & Co. The second, ChAd3-EBO-Z, was Italian. It was developed by an Italian company, bought by GlaxoSmithKline (GSK), and tested at CHUV. The Swiss institution’s efforts were praised in a recent article in the US magazine Newsweek, which ranked the CHUV as one of the world’s top 10 hospitals. “Both vaccines have the same technology platform,” Blaise Genton says, “but they use a different viral vector.” The one tested at the CHUV comes from a chimpanzee, while the one in Geneva is from the vesicular stomatitis virus of bovine origin. Both vaccines contain the same protein from the Ebola virus that generates antibodies and protects the vaccinated subject from the disease.
“We developed the protocol together and then compared our findings.”
The first step consisted in preclinical studies conducted on mice and rabbits. They have to survive and not develop major problems after being injected with a dose 10 to 100 times higher than what would be administered to a human. “The animals must not suffer from any serious side effects, and their offspring must not develop any problems. That generally takes a year or two. When we observed that the animals were doing well and had a significant immune response, we moved to initial testing on humans, a Phase 1 study.”
As part of the study, the Italian vaccine was tested in Lausanne on about 100 people. “The purpose of this step was to make sure that the vaccine did not cause any serious side effects,” the physician says. On 3 January 2015, the two teams had their initial findings: both vaccines were safe and produced an excellent immune response. They were then deployed in Phases 2/3 among the target population in Africa – the Italian vaccine in Liberia, and the Canadian vaccine in Guinea and Sierra Leone – to check their safety and immunogenicity, i.e. their capacity to elicit a measurable immune response.
Phase 3 was conducted to check that the vaccine prevents the disease in the environment where the virus is present, on thousands or even tens of thousands of people. For the Italian vaccine, this phase took place in Liberia starting on 15 February 2015. “This was when the vaccine’s safety and effectiveness were checked,” Blaise Genton says. In the field, studies were conducted by diverse organisations: local governments, which were “very involved”, and the NGOs Médecins Sans Frontières and American National Institute of Health (NIH).
“There were a few minor concerns with the Canadian vaccine at first. For example, some people experienced pain in the joints, but everything was fine after a few adjustments were made,” Blaise Genton explains.
The Ebola outbreak in Liberia ended before the effectiveness of the CHUV-tested Italian vaccine could be proved. “And that was great news. That means that the other prevention strategies against the virus – like isolating anyone with a fever and testing them for Ebola, or not touching the deceased without protective gear – were effective,” the doctor points out.
Meanwhile, the Canadian vaccine was tested in a Phase 3 clinical trial in Guinea and Sierra Leone. It was administered to more than 2,000 people to prevent the virus from spreading, and that enabled its approval. Its virtually 100% effectiveness rate, if given early enough, was proved, as was its utility in protecting healthcare staff and contacts of people with Ebola.
“Now, we vaccinate all contacts of confirmed victims as well as contacts of contacts. Basically, entire villages, because there’s a tertiary chain of transmission,” Blaise Genton says.
Although the effectiveness of the Italian vaccine could not be demonstrated due to the end of the Ebola outbreak in Liberia, “it is reasonable to believe that it also protects against the disease, given the similar immune response to the Canadian VSV vaccine,” he says, as highlighted in the British medical scientific journal, The Lancet.
In the Democratic Republic of Congo (DRC), where Ebola is currently raging, the Canadian vaccine is used as part of research protocols. That’s what we call “compassionate use”. However, the Italian vaccine is still being developed to create a vaccine that protects against several strains of the Ebola virus in addition to the Zaire strain that hit West Africa.
Until today, more than 3,000 people have been infected in the tenth ongoing epidemic in DRC. Over 90% of eligible people consented to vaccination, says WHO spokesperson Tarik Jasarevic. “But insecurity, the community’s distrust of foreigners, political instability, internal conflict, and of course the targeting of healthcare centres by rebels, mean that not everyone who should be vaccinated is. The DRC is facing one of the most complex humanitarian emergencies in the world.”
Developing the vaccines was expensive, about 500 million Swiss francs.
“But when we develop a technology platform for a vaccine, the information can be used in other research,” Blaise Genton points out. The WHO has now decided to split the doses of the Canadian vaccine tested in Geneva because the immune response was still good when only half the amount was injected. A half-dose is administered to people at high risk, and those at a lower risk are given a fifth of the dose. “We were all working almost 24 hours a day, 7 days a week during those months from late 2014 to early 2015. And the stress was compounded as all this was happening during the Christmas holiday period,” the doctor says. “But the experience showed that when there is a health emergency, quick and efficient mobilisation is possible.”
Mainly present in central and western Africa, the disease caused by the Ebola virus is zoonotic, meaning that it is transmitted from vertebrate animals to humans. Its natural hosts are bats, but primates and some antelopes can be intermediate hosts. Humans are indirectly infected by ingesting contaminated fruit, monkeys or antelopes, or via contact with bats and their excrement. The virus can also be transmitted directly through the bodily fluids (blood, vomit and faeces) of infected humans or animals, either alive or dead. The virus has an incubation period ranging from 2 to 21 days. The disease begins with a severe fever, sore throat and headache, muscle and abdominal pain, as well as diarrhoea and overall fatigue. The infection can become serious with bleeding and the failure of vital organs (liver, kidneys, heart, lungs). People with Ebola are contagious after the onset of symptoms, and the disease causes death in about half of cases.