By Kemo Cham
STRIVE (Sierra Leone Trial to Introduce Vaccine against Ebola) is one of several trials conducted during the 2014 Ebola outbreak in West Africa. Other trials were held in Guinea and Liberia which, like in Sierra Leone, were seriously affected by the deadly epidemic that ended up claiming over 11,000 lives by the time it was declared over by the World Health Organisation earlier this year.
Late last month experts, representing the government of Sierra Leone, the Ministry of Health and Sanitation (MoHS), the University of Sierra Leone and the United States Centres for Disease Control (CDC), converged at the Bintumani Hotel in Freetown to celebrate “a successful study”.
Politico talked to Dr Barbara Mahon [MD, MPH], the CDC’s Lead in STRIVE, on the progress of the study and its future.
Please read on…
Politico: In late August you [STRIVE team] gathered at the Bintumani Hotel. What that was about?
Mahon: That was a meeting to provide a final update on STRIVE and to share some of the current high level results. We talked about how SREIVE has completed follow up of more than 8, 000 volunteers who were vaccinated. There are a few women who became pregnant after vaccination that are still being followed.
Politico: Were these women part of the study?
Mahon: They were part of the study, they became pregnant after been vaccinated and we are following them until they deliver. But the main follow up of the people who were vaccinated has been completed.
Among those 8, 000 people [there was] no serious adverse event related to vaccination. So that provides actually the largest safety experience with this vaccine and it could be really important as part of the compilation of all of the information on the vaccine so that it can be submitted by the manufacturer for licensing.
Politico: You just said some women got pregnant during the trial. Was that anticipated?
Mahon: Well, women were counseled not to become pregnant until two months after vaccination. All of them had a pregnancy test at the time of vaccination. This is precaution. There is no known risk but to be cautious they were counselled not to become pregnant until two months afterwards. As you know sometimes things don’t go as planned and some did become pregnant and we are following them to see how their pregnancies are going.
Politico: When you said you are following them, are you looking specifically for something?
Mahon: They are being followed until the baby is born and the baby can be examined.
Politico: I remember in February 2015, you [STRIVE team] were part of a team of experts who made a presentation about a planned vaccine study. Back then it was called the Sierra Leone Ebola Vaccine Evaluation Study (SLEVES). How are these two related?
Mahon: I wasn’t here then and I am not familiar with that acronym. STRIVE is the only study CDC is sponsoring here.
Politico: What vaccine candidate are we talking about here?
Mahon: The technical name is the rvsvZEBOV. This is the vaccine that was shown to be effective… A trial using the same vaccine was conducted in Guinea and the preliminary result from that study showed effectiveness against Ebola.
Politico: Reports from the Bintumani meeting cited officials describing the trial as successful. What exactly did you mean?
Mahon: I think it’s really important to understand that more than 8, 000 volunteers took the vaccine and there was no serious adverse events that related to the vaccine in that entire group of people. So that’s one of the most important results of the study.
There is another result that is pending and we expect it to be available in the early part of next year. And that is a sub group of the participants in the study who gave blood specimen before they were vaccinated and a specified time period after they were vaccinated to be tested for antibodies, the immune response against the vaccine, and so using both results, it will cast light on the immune response to the vaccine and on the duration of the protection that might be given by the vaccine.
This is a sub set of people who not only took the vaccine but also gave blood specimen to test the effect of the vaccine on the immune system.
Politico: I see. Two in one study. Is that it?
Mahon: Yes, those people gave information about safety, but they also are going to be giving information about the body’s immune response to the vaccine.
Politico: And this was part of the original plan of the study?
It was part of the protocol for the study. The protocol was developed over time and this became increasingly important as the number of cases of Ebola decreased. It’s only good that Ebola was controlled in Sierra Leone. But because there were no Ebola cases in STRIVE participants, STRIVE is not going to be able to show that the vaccine prevents Ebola. But this immunogenicity study can show that the vaccine spurred the development of a response that could be protective.
Politico: When the 2014-2016 epidemic was spreading, it made sense to conduct a study like this, because there were test cases which we know are needed for such. Now there are no test cases. What does this mean for the study?
Mahon: In the Guinea study with the same vaccine there were test cases. And so they were able to demonstrate a decrease in Ebola cases. What STRIVE adds to that is the large safety experience as well as the ability to measure the immune response to the vaccine. So you put it all together, all of that information will be part of the application for licensing.
Politico: And the Guinea study is a part of the Sierra Leone study?
Mahon: No, the Guinea study is a separate study, sponsored by WHO, conducted in collaboration with Guinean colleagues.
Politico: I mean was it the same vaccine?
Mahon: Yea, it’s the same vaccine. There is a third study in Liberia that’s called PREVAIL that also included the same vaccine, as well as another vaccine.
Politico: And at the end of the day, approval will take account of all these results?
Politico: The fact that Ebola was waning was a concern, wasn’t it?
Mahon: Well, from a very narrow point of view of the study, it limited the ability to demonstrate disease prevention from the vaccine.
We can never call waning Ebola a problem, it’s a good thing. I can’t even say that… It’s only good. And STRIVE is still able to provide this really important information.
Politico: I understand studies were conducted outside West Africa on the same candidate vaccine. Is that so?
Mahon: This vaccine has been studied in volunteers in many countries, in Africa, in Europe, in the United States… It wasn’t the exact same trial, but the vaccine has been used widely in volunteers from many countries.
Politico: These were before the 2014 outbreak?
Mahon: Before and after.
Politico: The relationship between the trials in Sierra Leone and Guinea is now quite clear. In the other countries, what was it looking at?
Mahon: All of the studies used slightly different scientific approaches but all were attempting to show an effect on the disease and to gather information on safety. And I believe that they all included measurement of antibodies. The different studies ultimately will provide different information on the vaccine that can be used to support the application for licensing.
Politico: STRIVE is funded by US government, but who actually owns this particular candidate vaccine?
Mahon: It’s owned by Merck [Pharmaceutical Company] with licensing from another company. Merck is the manufacturer.
Politico: How is the rvsvZEBOV different from other candidate vaccines?
Mahon: It’s what is called a vector vaccine, meaning that a small piece of Ebola virus that cannot cause Ebola is inserted into a different virus that’s harmless. Other vaccines have taken a different approach using different vectors and other difference approaches.
Politico: We were told that in this trial you are not using placebos. Please explain that.
Mahon: There was a great deal of thought and discussion about the design of the study and whether to use placebos or not… It think it will be fair for me to say that there was a concern that those people who received a placebo might falsely assume that they were protected and might not be as careful in protecting themselves from Ebola using PPEs (Personal Protection Equipment) and using appropriate precautions in the hospitals.
Politico: We know that this [study] is a collaboration between the MoHS, the University of Sierra Leone and the CDC. Please tell us the specific role of each party in this.
Mahon: COMAHS [College of Medicine and Allied Health Sciences] is the lead for the study. Dr [Mohamed] Samai is principal investigator. And COMAHS is involved in every aspect of implementation of the study. CDC is the sponsor. CDC has played a more active role in supporting COMAHS than a sponsor often does, in recognition that this sort of activity is new for Sierra Leone, to build capacity, exchange information, and so forth.
So CDC has been very involved as well in supporting COMAHS in implementation.
The Ministry of Health from the start directed CDC to work, first and foremost, with COMAHS because, of course, their attention had to be primarily focused on response to Ebola. But they have also been involved in reviewing protocol and approving human subject protection and the other aspects of the study. So it really is a three way partnership.
Politico: When you said COMAHS is the lead. I really will like to know what they do. I am asking because the assumption is that local expertise, in terms of the technical work, doesn’t exist.
Mahon: That’s not so. There is a great deal of talent and knowledge of clinical studies. Dr Samai is an experienced expert investigator and there are others. But you are right, capacity is limited here and so CDC has done what we can to support with technical assistance, to support with training as needed and to be available for consultation.
Politico: Initially, during the launch of the study back last year, we were also told that 6, 000 people were to participate. Now the number has gone to 8, 000. How did that happened?
Mahon: Because Ebola was decreasing, there was a time when it appeared that if more people were involved there might still be the opportunity to demonstrate an effect against the disease. So protocol amendment was written and submitted for ethical review, human subject review, in Sierra Leone and in the US and the increase was approved, in part because at that point there was some information on safety and the experience at that point had been very good.
Politico: There are no studies like this that don’t come with side effects, although you have indicated there were no serious adverse events. But what are the instances have you had to deal with?
Mahon: It’s really important to be clear on this. There were no serious adverse events, which means serious adverse events related to the vaccine. And so there was no hospitalization, no deaths, no events that would cause a permanent disability, and so forth.
The vaccine does cause reactions, it causes muscle pains, headache, fever, it can cause aches in the joints, and the events that we saw here in Sierra Leone…many people experienced those. They got better on their own within one to two days and they were not serious adverse events. They didn’t lead to hospitalization. They didn’t lead to more serious outcomes.
So absolutely the vaccine can cause some vaccine reactions, as what all vaccines do. But thankfully we didn’t see any serious response that were related to the vaccine.
Profile of Dr Mahon from the CDC
Dr Mahon received her MD and clinical training in pediatrics from the University of California, San Francisco and her MPH from the University of California, Berkeley. She trained in CDC’s Epidemic Intelligence Service (EIS). Dr. Mahon is deputy chief of the Enteric Diseases Epidemiology and
Surveillance Branch at the Centers for Disease Control and Prevention (CDC). The branch is responsible for national surveillance for enteric diseases. It conducts epidemiologic studies of the burden, trends,
and food source attribution of foodborne diseases caused by
Listeria, Salmonella, and E. coli O157, among other pathogens. The branch’s work also focuses on vulnerable populations, including older
adults, young children, and other groups, with the goal of creating knowledge needed to protect people by preventing disease. Dr. Mahon has a broad background in infectious disease epidemiology, having
worked on foodborne diseases, vaccine - preventable diseases, and sexually transmitted diseases in academic and industry positions as well as in government.
(C) Politico 2016