Why Ebola Vaccine May Not Stop Epidemic

Professor Adrian Hill, Director leader of the trials for the experimental Ebola vaccine holds a vial of the vaccine in Oxford, England Wednesday Sept. 17, 2014.

Professor Adrian Hill, Director leader of the trials for the experimental Ebola vaccine holds a vial of the vaccine in Oxford, England Wednesday Sept. 17, 2014. Steve Parsons/AP

The earliest human trials—that is, initial safety studies in small numbers of volunteers—are underway.

Dr. Jesse Goodman, is a specialist in infectious diseases and the director of COMPASS, a Georgetown University center that informs policy on public health and product development. Until February 2014 he was the chief scientist of the US Food and Drug Administration (FDA). Goodman spoke with Ebola Deeply about the challenges of developing Ebola vaccines and experimental treatments.

How are the control tests for Ebola vaccines going?

The earliest human trials—that is, initial safety studies in small numbers of volunteers—are underway. There are several more vaccines in production that have not yet been tested in human beings, but which appear to be effective in primates. One is made by a company called Profectus, and the other is made using Modified Vaccinia Ankara (MVA), which has been used in a number of vaccines including smallpox. In this case it’s designed to produce non-infectious virus-like particles that display the Ebola virus glycoprotein.

We just don’t know how long it’s going to take for them to be declared safe, or even if they’ll be effective. People are working very quickly to get initial human studies done, and also to scale up potential manufacturing for the leading candidates. But it’s a complex business and none of these vaccines has so far been manufactured in large amounts. Even by next spring is pretty optimistic; things usually take longer than people project.

What are the biggest challenges, besides the time constraints, of producing an Ebola vaccine?

These are complex vaccines that involve a live virus and you always have to have very well-controlled production. Cost is one factor: I think it’s hard to predict, but these are not going to be inexpensive to produce. However, many public health experts have said that if we have a safe and effective vaccine, the cost mustn’t get in the way of it reaching communities.

With all experimental treatments, including vaccines, it’s really important not to make presumptions that they will work. It would really be a shame if we’re not able to learn what works and what doesn’t, for the next outbreak or if this one continues over an even longer period. A vaccine could be a really important tool, but if we don’t have solid studies that show that it works and is safe, I think it would be really problematic just to immunize huge numbers of people with a vaccine we don’t understand.

It’s important for people to realize that a lot of vaccines in testing don’t pan out the way we hope. If you’re going to give them to huge numbers of healthy people, it’s really important to have confidence and to be able to explain any adverse affects to people; to say, we did a study of “x” amount of people and it reduced Ebola infection by “x” percent. We’d hope it would be 100%, but at this point we don’t know what is possible. One HIV vaccine that was trialed was shown to actually increase acquisition of HIV.

It’s also important to consider the mistrust that people feel when they don’t know enough about a vaccine and how it works. There have been polio vaccine campaigns that were seen as an attempt to kill people, and obviously they are not, so I think it’s very important to inform as much as you can, and forge that trust. Similarly, if control studies are done in West Africa, it’s very important that the countries themselves use effective communication with participants. Healthcare workers have both a higher risk of disease and are likely to better understand that something is experimental. So it may be that such people are more interested in taking part in the studies.

What are your thoughts on the potential of other experimental treatments, such as the convalescent plasma that US survivors have received?

A lot of the enthusiasm for convalescent plasma is based on just one paper from an epidemic nine years ago in which they described seven patients receiving convalescent plasma and recovering. However, that same paper also mentions that five other patients had received it in another center, and they all died. The paper also points out that there were things about those seven patients that could well have contributed to their survival. With convalescent plasma, we just don’t know. In non-human primates, there is some evidence that it works, but the results have been conflicting.

The strategy is that the plasma provides the opportunity to transfer antibodies against the virus from somebody who has recovered to somebody who is sick, and probably for that to work, it would need high amounts of antibodies. Not every survivor has that. But the advantage of convalescent plasma is that we don’t have to wait for a testing process to study it. We just can’t tell if the survivors of this outbreak who received plasma would have recovered anyway. There’s a pretty good sense that supportive medical care does a lot to help. More than three-quarters of people who have been able to get to that kind of supportive, intensive care, such as IV, have survived. Convalescent plasma, in addition to that, is not going to hurt.

Some Liberian doctors say they have had some success in treating patients with anti-retroviral drugs (ARVs) designed for HIV/AIDS patients. Is there any evidence that this strategy works?

My understanding is that outside of descriptions from Liberia, there’s not much more information about the success of ARVs. People are trying things out in real life that have worked in the test tube, or on non-human primates. We need to be aware that some things can potentially hurt people. One experimental Ebola treatment, an interfering RNA product made by Tekmira, was put on hold by the FDA during safety studies because participants developed cytokine reactions. Now if you give something like that to an Ebola patient, it can be hard to distinguish the adverse effect from the disease itself.

Medics working on this outbreak are reporting symptom variation. That’s to say, one person can recover fairly quickly from Ebola, while another can reach the hemorrhagic stage. Why do you think Ebola affects people differently?

I think that’s a very good question and, to be honest, no one knows the answer. In the past this disease has broken out in situations where it has been difficult to do studies. There just isn’t a whole lot of information. But my guess is that we see this in many other acute infectious diseases, where there’s a range of outcomes.

One factor is probably early diagnosis and supportive treatment. Researchers at Emory described a group of patients who hadn’t started supportive care early as being very dehydrated and behind in their fluid replacements, such as potassium and calcium. Early diagnosis and aggressive hydration are things that can be done in the affected countries.

Age is also a factor; younger people generally fare better, as do those without underlying diseases. Another factor could be the nutritional status of the host. I think we can presume that at least some of the people infected in some areas may have poor nutritional status. And that’s clearly been shown to have an impact on immune system response. It could also be the amount of virus that you’re exposed to.

What do we know about the long-term effects of Ebola? What can survivors expect further down the line?

Some of the most useful descriptions of long-term effects come from the 1995 outbreak in the Democratic Republic of Congo. The CDC did a series of studies following survivors over longer periods of time and found that, unsurprisingly for a very severe infection, many survivors have prolonged fatigue. They also described people as having muscle and joint aches. Other long-term symptoms were comparatively rare. But again, this disease has just not been that well studied and it may be that with this much larger epidemic and hopefully more survivors, we’ll hear about other long-term problems.

This outbreak has already continued for much longer than early projections in West Africa indicated. How optimistic are you that the epidemic can be contained?

I’m very disturbed by the modeling and how slow the global response has been, despite the US and other countries stepping up to build capacity. It’s very challenging to do that and it’s taking longer than everybody hoped. From a perspective of distance, it would seem that the affected countries do have an opportunity to bring this to a halt, but there are so many barriers, such as all the things that you want to do when someone you love is sick: care for each other, touch each other.

I think if communities can find ways to be caring without placing themselves at risk, then the impact could be huge. But none of that is easy for Westerners to go to a country and institute; local engagement is so critical. I’m not totally pessimistic because I think that people are smart, but this is a really bad infectious disease and I think developing vaccines and treatments is the right thing to do.

Countries with strong health infrastructure like the US can certainly contain their cases, but I do worry about many other countries in the world.

We’re very fortunate, in a way, to have so many vaccines in process, and my guess is that one or more of them will work out, but it may not be one of the first two. I don’t think anyone should rely on it.

This post originally appeared at Ebola Deeply