Center for Infectious Disease Research and Policy (CIDRAP)
By: Robert Roos, News Editor
October 22, 2014
Large clinical trials that would put Ebola vaccines in the arms of thousands of West Africans may begin as early as January, depending on the outcome of small preliminary trials under way now or soon to start, a World Health Organization (WHO) official said at a press conference today.
A January start for major West African trials would be about 2 month later than the same official, Marie-Paule Kieny, PhD, a WHO assistant director-general, projected in early September. It also differs from a prediction made last week by a US official, Peter Jahrling, PhD, of the National Institute of Allergy and Infectious Diseases, that a large trial of two vaccines could begin in Liberia in December.
Kieny said results of small safety and immunogenicity trials for the two leading candidate vaccines are expected in December. Depending on those findings, she said, large efficacy trials involving tens of thousands of volunteers could start in January. In early September she had suggested that some doses might be available for healthcare workers as early as November.
"I'm not suggesting that there will be mass vaccination at population levels starting in January 2015," Kieny said today. "When I talk about vaccine deployment in these countries, I'm talking about tens of thousands of doses."
"There's still a possibility that we'll fail . . . but everybody is putting things in order to be able to deploy to West Africa in January," she said. "This will most likely be in the form of efficacy trials, but to have a response as quickly as possible these trials need to be quite large and enroll quite quickly."
She couldn't predict how soon a mass vaccination campaign might be possible.
One of the two leading vaccine candidates is being developed by the US government in partnership with GSK. It involves an adenovirus engineered to carry an Ebola virus protein and is called ChAd3.
The other leading candidate was developed by the Canadian government and has been licensed to a small company, NewLink Genetics, based in Ames, Iowa. Called VSV-EBOV, It uses an Ebola virus protein spliced into a vesicular stomatitis virus (VSV).
The US-GSK vaccine is in small phase 1 clinical trials now in the United States, the United Kingdom, and Mali, Kieny said. A somewhat larger trial is due to start in Lausanne, Switzerland, by the end of this month or early November, she added. The preliminary trials aim to assess the vaccines' safety and immunogenicity.
Two very small trials of the Canadian vaccine are under way in the United States at Walter Reed Hospital and the National Institutes of Health, Kieny reported. Further trials are due to start soon in Hamburg, Geneva, Gabon, and Kenya, she added. The trials will use a wide range of doses to assess immunogenicity.
"We expect to have initial results . . . about safety and immunogenicity to have a choice of a dose level by the end of this year," she said.
In August the Canadian government promised to give 800 vials of VSV-EBOV to the WHO. Kieny reported that the vials were expected to arrive in Geneva today, after a strike-related airline delay. From there they are to be distributed to the clinical trial sites.
Kieny stressed that it is crucial to determine the correct dose level to elicit a strong immune response while maximizing the number of doses available. Officials from the Ebola-affected countries and nations involved in vaccine development will meet Oct 23 to discuss the vaccine strategy.
Official grilled about GSK comments
Kieny was questioned sharply about comments last week by Ripley Ballou, MD, GSK's director of Ebola vaccine research. In media reports, he was quoted as saying that safety and efficacy data needed for the use of the GSK vaccine won't be available before the end of 2015. He also said he didn't think the vaccine should be seen as "the primary answer" to the epidemic and that it would take till well into 2016 to make large amounts of it.
Responding to the questions, Kieny said, "I don't know how much vaccine will be available in 2015, but it will be available in 2015 for sure."
She was also asked about reports that GSK discussed its Ebola vaccine with the WHO in March, when the outbreak surfaced, and that the company and the agency then agreed that the vaccine was not needed.
She replied that she received a message form Ballou in in March that the company was interested in moving forward with the vaccine. "We never said we weren't interested, but the general understanding at that time was that this vaccine would not be developed in time to have an effect in that outbreak. At that time nobody thought it would become the outbreak we have now."
In other comments, Kieny said discussions are in process but no decisions have been made about which groups should be the first to get the vaccines when they become available. Possible priority groups include healthcare workers, other front-line workers, and close contacts of case-patients, she noted.
Also unsettled is whether to use placebo groups in Ebola vaccine and drug trials, she said, acknowledging that some experts have argued that it would be unethical to give volunteers a placebo if they're at risk for contacting a disease that has a very high fatality rate.
"There are now discussions among methodologists to see if they can come up with designs for these trials which can bring both the utility aspect and the ethical aspects into consideration," she said.
Convalescent serum update
In other comments, Kieny indicated that it will still be a few weeks, at least, before there is any appreciable use of blood serum from recovered Ebola patients to treat sick patients in West Africa. In September the WHO had suggested that using convalescent serum might be a promising way to help patients in the near term, while vaccines and drugs are awaited.
She said partnerships are forming in the three Ebola-hit countries-Guinea, Liberia, and Sierra Leone-to build the capacity to extract plasma and use it for treatment. "The partnership moving quickest is in Liberia, where we hope that in coming weeks there will be a facility set up to collect and treat the blood and be able to process it for use," she commented.
She also spoke of "a number of initiatives" to move toward clinical trials of Ebola drugs. She gave few details on those, but did mention that the French government is working to set up a trial in Guinea of favipiravir, an antiviral developed by a Japanese company.
In response to a question, Kieny said she is not aware of anyone who has recovered from Ebola and later been re-infected. Some experts have suggested that Ebola survivors should be recruited to work on the front lines of the epidemic, since they are presumably safe from the disease.