World Health Organization

Final trial results confirm Ebola vaccine provides high protection against disease

An experimental Ebola vaccine was highly protective against the deadly
virus in a major trial in Guinea, according to results published today
in The Lancet. The vaccine is the first to prevent infection from one
of the most lethal known pathogens, and the findings add weight to
early trial results published last year.

The vaccine, called rVSV-ZEBOV, was studied in a trial involving 11,841
people in Guinea during 2015. Among the 5,837 people who received the
vaccine, no Ebola cases were recorded 10 days or more after
vaccination. In comparison, there were 23 cases 10 days or more after
vaccination among those who did not receive the vaccine.

The trial was led by the World Health Organization, together with
Guinea’s Ministry of Health, Medecins sans Frontieres and the Norwegian
Institute of Public Health, in collaboration with other international
partners.

“While these compelling results come too late for those who lost their
lives during West Africa’s Ebola epidemic, they show that when the next
Ebola outbreak hits, we will not be defenceless,” said Dr Marie-Paule
Kieny, WHO’s Assistant Director-General for Health Systems and
Innovation, and the study’s lead author.

The vaccine’s manufacturer, Merck, Sharpe & Dohme, this year received
Breakthrough Therapy Designation from the United States Food and Drug
Administration and PRIME status from the European Medicines Agency,
enabling faster regulatory review of the vaccine once it is submitted.

Since Ebola virus was first identified in 1976, sporadic outbreaks have
been reported in Africa. But the 2013-2016 West African Ebola outbreak,
which resulted in more than 11,300 deaths, highlighted the need for a
vaccine.

The trial took place in the coastal region of Basse-Guinée, the area of
Guinea still experiencing new Ebola cases when the trial started in
2015. The trial used an innovative design, a so-called “ring
vaccination” approach – the same method used to eradicate small pox.

When a new Ebola case was diagnosed, the research team traced all
people who may have been in contact with that case within the previous
3 weeks, such as people who lived in the same household, were visited
by the patient, or were in close contact with the patient, their
clothes or linen, as well as certain “contacts of contacts”. A total of
117 clusters (or “rings”) were identified, each made up of an average
of 80 people.

Initially, rings were randomised to receive the vaccine either
immediately or after a 3-week delay, and only adults over 18 years were
offered the vaccine. After interim results were published showing the
vaccine’s efficacy, all rings were offered the vaccine immediately and
the trial was also opened to children older than 6 years.

In addition to showing high efficacy among those vaccinated, the trial
also shows that unvaccinated people in the rings were indirectly
protected from Ebola virus through the ring vaccination approach (so
called “herd immunity”). However, the authors note that the trial was
not designed to measure this effect, so more research will be needed.

“Ebola left a devastating legacy in our country. We are proud that we
have been able to contribute to developing a vaccine that will prevent
other nations from enduring what we endured” said Dr KeÏta Sakoba,
Coordinator of the Ebola Response and Director of the National Agency
for Health Security in Guinea.

To assess safety, people who received the vaccine were observed for 30
minutes after vaccination, and at repeated home visits up to 12 weeks
later. Approximately half reported mild symptoms soon after
vaccination, including headache, fatigue and muscle pain but recovered
within days without long-term effects. Two serious adverse events were
judged to be related to vaccination (a febrile reaction and one
anaphylaxis) and one was judged to be possibly related (influenza-like
illness). All three recovered without any long term effects.

It was not possible to collect biological samples from people who
received the vaccine in order to analyse their immune response. Other
studies are looking at the immune response to the vaccine including one
conducted in parallel to the ring trial among frontline Ebola workers
in Guinea.

“This both historical and innovative trial was made possible thanks to
exemplary international collaboration and coordination, the
contribution of many experts worldwide, and strong local involvement,”
said Dr John-Arne Røttingen, specialist director at the Norwegian
Institute of Public Health, and the chairman of the study steering
group.

In January, GAVI, the Vaccine Alliance provided US$5 million to Merck
towards the future procurement of the vaccine once it is approved,
prequalified and recommended by WHO. As part of this agreement, Merck
committed to ensure that 300,000 doses of the vaccine are available for
emergency use in the interim, and to submit the vaccine for licensure
by the end of 2017. Merck has also submitted the vaccine to WHO’s
Emergency Use and Assessment Listing procedure, a mechanism through
which experimental vaccines, medicines and diagnostics can be made
available for use prior to formal licensure.

Additional studies are ongoing to provide more data on the safety of
the vaccine in children and other vulnerable populations such as people
with HIV. In case of Ebola flare-ups prior to approval, access to the
vaccine is being made available through a procedure called
“compassionate use” that enables use of the vaccine after informed
consent. Merck and WHO’s partners are working to compile data to
support license applications.

The rapid development of rVSV-ZEBOV contributed to the development of
WHO’s R&D Blueprint, a global strategy to fast-track the development of
effective tests, vaccines and medicines during epidemics.

NOTES TO EDITORS

The rVSV-ZEBOV trial is funded by WHO, with support from the Wellcome
Trust; the United Kingdom Department for International Development; the
Norwegian Ministry of Foreign Affairs; the Norwegian Institute of
Public Health through the Research Council of Norway; the Canadian
Government through the Public Health Agency of Canada, Canadian
Institutes of Health Research, the International Development Research
Centre and the Department of Foreign Affairs, Trade and Development;
and Médecins Sans Frontières.

The trial team includes experts from The University of Bern, the
University of Florida, the London School of Hygiene and Tropical
Medicine, Public Health England, the European Mobile Laboratories among
others. The trial was designed by a group of experts including the late
Professor Donald A. Henderson of John Hopkins University, who led the
WHO smallpox eradication effort by using the ring vaccination strategy.

Interim results of the trial were published in August 2015 and can be
accessed here:
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)61117-
5/abstract

VSV-EBOV was developed by the Public Health Agency of Canada. The
vaccine was licensed to NewLink Genetics, who in turn licensed it to
Merck & Co. The vaccine works by replacing a gene from a harmless virus
known as vesicular stomatitis virus (VSV) with a gene encoding an Ebola
virus surface protein. The vaccine does not contain any live Ebola
virus. Earlier trials have shown the vaccine to be protective in
animals, and be safe and produce an immune response in humans.

Analysis only included cases occurring 10 days after receiving the
vaccine to account for the incubation period of the Ebola virus.