In the race for an Ebola vaccine, the clear front-runner is the virus, which is expected to spread to tens of thousands of people in the coming weeks. But new competitors are now gearing up for human trials, and eventually the tables could turn. In the long run a vaccine could prove extremely important if, as some predict, the virus causing the current outbreak in West Africa will remain in circulation as a low-level “endemic” disease indefinitely.
The latest entry to the race comes from the Maryland-based
Illustration showing the Ebola virus-encoded glycoprotein trimers (pink) embedded in the host cell's... [+]
The big selling point the company emphasized is that the Novavax product is the only one designed to target the exact strain of Ebola that’s currently raging through West Africa. Experts disagree over whether this fact will make a difference because the parts of the virus that are relevant to vaccines are nearly identical across strains.
On the other hand, scientists working on the Ebola problem acknowledge they are in new territory and can’t be sure what will and won’t work until human trials are carried out.
The terminology describing strains and species of Ebola can cause some confusion. There are five species – the current outbreak being caused by a species known as Ebola Zaire. Within that species are several different strains. Biologists have analyzed genetic material from the strains and found that evolution has led to some variation. What that variation means and how it will influence the course of the outbreak is not well understood, partly because the process of biological evolution is unpredictable.
Some scientists at the conference – the 8th Vaccine and ISV Congress – were skeptical because the Novavax results came from mice. The company has begun trials in monkeys, however, which are considered much more relevant to humans.
Currently, several groups have tested vaccines in monkeys and found promising results.
Another vaccine candidate has been developed by Walter Reed Army Institute of Research collaborating with government scientists in Canada. Instead of a cold virus, it uses an altered cow virus called vesicular stromatitis virus, or VSV. This vaccine, too, has proven effective in monkeys.
Meanwhile, researchers at Thomas Jefferson University in Philadelphia have been working for the last four years on a modified rabies vaccine that in monkeys can protect against both diseases. Rabies kills more than 20,000 people every year in Africa, said lead researchers Matthias Schnell. He said they have proven their product works in monkeys and could be ready to start human safety trials by January. He has plans to partner with a major pharmaceutical company to scale up production of the vaccine, but as of this week, those plans are still being worked out.
Also in the race is
The Novavax researchers were able to more precisely target the virus behind the current outbreak because they started with the known sequence that makes up its genetic material. “We never touch a living organism in terms of the pathogen,” said Greg Glenn, senior vice president for research and development, in a phone interview. Instead, they synthesize the relevant genetic material from the sequence data. Then they use a cell culture made from insect eggs to create multiple copies of this genetic material and produce the Ebola proteins deemed most likely to prompt the immune system to mount protective action.
The delivery system is not an existing virus but a synthetic “nanoparticle”. “It looks like a virus from the immune system’s point of view,” said Glenn. He said that if the experiments in monkeys go well they could be ready to start safety testing in humans by January.
Schnell, who leads work on the combined Ebola and rabies vaccine, said that he doubts targeting the exact strain will matter for efficacy of the vaccine. “There’s no real benefit,” to targeting the genetic sequence of this outbreak, he said.
But biologist David Sanders, who has studied Ebola at Purdue University, said that it’s remotely possible the subtle difference between strains will make a difference. It’s true, he said, that the viral proteins that make up the key part of the vaccine are highly “conserved”, meaning they and the genetic material holding their blueprints have changed very little from one strain to another.
But there’s also part of the viral genetic material they call a “hypervariable region” because it seems to evolve more rapidly. Its role is less clear but Sanders said it may help the virus protect itself from the immune system and therefore may affect the way vaccines work.
Considering how little the scientists know about this virus, Sanders said it’s worth pursuing a vaccine that targets the specific strain circulating in West Africa. Having multiple vaccine candidates increases the chances that something will work, he said. “You have to be thinking about what can potentially go wrong.”
As many acknowledge, the fact that some candidates work in monkeys is no guarantee they will work safely in humans – a lesson the research community learned in attempting to create a vaccine against HIV. And no one knows how long these vaccines are likely to last, or whether there’s any chance they could protect people already exposed to Ebola but not yet sick.
Even if a vaccine proves safe and effective there are enormous hurdles in scaling up production and transporting it to the places where it’s needed. Glenn said his company’s system may be easier to scale up quickly if the vaccine proves safe and efficacious.
The bad news is that disease modelers predict that the death toll will likely explode over the coming weeks, affecting hundreds of thousands of people before any of these vaccines could be put to widespread use.
That doesn’t mean vaccines won’t still prove crucially important. Many scientists say the outbreak will eventually subside as it runs out of vulnerable people, much as a fire runs out of fuel, and people in the affected countries may change aspects of their behavior – such as spreading the disease by the washing of dead bodies.
After this outbreak subsides, the virus probably won’t disappear completely, some say, but will remain at a lower level, flaring up on occasion. So looking ahead, even if these vaccines take two years to test and scale up, they could end up saving thousands or even hundreds of thousands of lives.
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