In the wake of a meeting yesterday, the World Health Organization (WHO) announced today that a large efficacy trial of the two leading Ebola candidate vaccines may start in Liberia in December, a month earlier than the agency predicted just 3 days ago.
"We're talking about now starting in December and not January," Marie-Paule Kieny, PhD, told reporters at a press conference in Geneva. Citing an urgent vaccine development push by manufacturers, governments, and other partners, she added, "It shows how everything is pushed forward and the massive effort by everybody."
Kieny, the WHO's assistant director-general for health systems and innovation, also said hundreds of thousands of doses of Ebola vaccine may be available by June 2015, although that doesn't mean that mass vaccinations in West Africa could begin by that time.
Her announcement followed a meeting yesterday involving officials from Ebola-affected countries, governments sponsoring vaccine development, pharmaceutical companies, and nongovernmental organizations (NGOs).
Small phase 1 trials of the two most advanced vaccines are already under way or about to start at several sites, with results expected in December, Kieny noted, echoing previous statements. The trials aim to assess the vaccines' safety and immunogenicity at different doses.
"All is put in place by all partners to start efficacy trials in affected countries as early as December 2014," she said. She said the trials could involve 20,000 to 30,000 volunteers, some of whom would receive a control vaccine rather than an Ebola vaccine, an approach that's likely to be controversial.
In a press release, the WHO said the efficacy trial protocols will be "adapted to take into consideration safety and immunogenicity results as they become available."
Multiple vaccines in pipeline
One of the two leading candidate vaccines was developed by the US government in partnership with GSK, and the other was created by the Public Health Agency of Canada and has been licensed to NewLink Genetics Corp., Ames, Iowa.
The US-GSK vaccine, known as ChAd3 ZEBOV, uses a chimpanzee adenovirus with a Zaire Ebola virus gene spliced into it, while the Canadian vaccine uses a vesicular stomatitis virus (VSV) to carry an Ebola gene and is called VSV-ZEBOV.
Close behind those two products in the development race, said Kieny, are at least five other experimental Ebola vaccines, which she expects will be in clinical trials in the early months of 2015.
The companies developing the Ebola vaccines "are committing to ramping up the production capacity to millions of doses to be available in 2015, with hundreds of thousands ready in the first half of next year," she said. "To make this a reality, regulatory authorities in countries where the vaccines are made and in Africa will need to work closely with manufacturers on extremely short timelines to overcome a number of hurdles in the licensing and regulation of the vaccines."
Kieny also said community engagement to promote acceptance of the vaccines will be a key part of the Ebola vaccine enterprise. "Work should be scaled up urgently in partnership between local communities, national governments, NGOs and international organizations," the WHO release put it.
Although the timing is hard to predict, officials hope to have initial findings from the efficacy trials in hand around April of next year, said Kieny.
Three-armed trial envisioned
She said the first efficacy trial is likely to be in Liberia, where plans call for a trial with three arms—one for each of the two Ebola vaccines and one for a control vaccine. Planning is also under way for a trial in Sierra Leone, with either two or three arms, she added.
However, she also indicated there's some doubt as to whether both of the leading vaccines will be ready to test in a large trial at the same time. She said that for the Canadian vaccine, much less is known about what an appropriate dose would be.
There are no firm plans for a trial in Guinea at this point, Kieny said, commenting, "There seems to be less intense transmission in Guinea right now than in the other two countries, so we're more focused on those."
She said it wouldn't accomplish much to duplicate in Guinea a trial that's being conducted elsewhere, but officials are discussing what questions an additional trial might address and how to go about doing it.
Experts support placebo use
Some medical experts and ethicists have argued against using a placebo control in the Ebola vaccine trials, saying it would be unethical to withhold a possibly protective vaccine from people who may be exposed to such a deadly disease.
But Kieny said, "Most voices we hear are saying that for a vaccine trial, in view of the added speed that such a design requires in terms of demonstrating definite efficacy, this [a placebo] would be the preferred design."
Those who don't receive an Ebola vaccine would get another vaccine (rather than a dummy injection), so they would have some benefit, and all the volunteers will be followed closely so they could receive early treatment if they get sick, she added.
As for when mass vaccinations could begin in West Africa, Kieny indicated it's unlikely but not impossible that that could happen before June. If a vaccine proves effective, if the epidemic curve justifies mass vaccination, and if enough doses were available, it could happen, she said.
She also commented that an effective vaccine might make an impact on the epidemic even if the kinds of responses now under way succeed in reversing the disease's spread before a vaccine is available in quantity.
In other comments, Kieny said:
- Given that safety information on the Ebola vaccines will be limited, the United Kingdom has proposed establishing a fund to compensate anyone who is injured by an Ebola vaccine.
- A Russian representative at the WHO meeting said three Ebola vaccines are in development in Russia, based on an adenovirus, a lentivirus, and an attenuated influenza virus. One or more of these could be starting clinical trials soon.
- Healthcare workers will be among the first to receive an Ebola vaccine, but decisions have yet to be made about other priority groups. Modeling studies are in progress to determine which groups should be targeted for maximum impact.
Meanwhile, a media report today said that Russia has started producing a trial batch of a vaccine to be tested against Ebola virus in Africa.
The head of Yunona Pharmaceutical Holdings, Aleksandr Petrov, said the vaccine would be sent to Africa "in the next few days" for testing, according to the report from Bernama, Malyasia's national news agency. The story cited Russia's Itar-Tass news agency as its source.
Petrov said the vaccine, called Triazavirin, has been found to be effective against influenza, tick-borne encephalitis, and other viruses.
Audio recording of Oct 24 WHO briefing (note: may open slowly)
Related Oct 21 CIDRAP News story
Oct 24 Bernama story