•We’ll Not Be Defenceless If Next Occurrence Hits – WHO
By Chioma Umeha
In the wake of Ebola
epidemic in West Africa, the World Health Organization (WHO) convened an urgent
meeting on September 29 and 30, 2014, to assess the efforts under way to
evaluate and produce safe and effective Ebola vaccines as soon as possible.
The 70 scientists,
public health officials, and representatives from industry and regulatory
bodies who gathered in Geneva discussed two vaccine candidates at length –
cAd3-EBOV (cAd3), from GlaxoSmithKline (GSK) and the U.S. National Institute of
Allergy and Infectious Diseases (NIAID), and rVSV?G-EBOV-GP (rVSV), from
NewLink Genetics and the Public Health Agency of Canada.
Several other vaccine
candidates were at earlier, preclinical stages in the development pipeline at
that time.
This is over two years
ago.However, light seems to have appeared at the end of the tunnel as the world
health body on Monday confirmed the first Ebola vaccine.
An online news agency
said that an experimental Ebola vaccine was highly protective against the
deadly virus in a major trial in Guinea, according to results published 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 in 10 days or more after
vaccination. In comparison, there were 23 cases in 10 days or more after
vaccination among those who did not receive the vaccine.
The trial was led by the
United Nations health body, 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 to 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-Guinee, 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 three 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 three-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 six
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 3, 00,000 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 the WHO’s partners are working to compile
data to support licence applications.
The rapid development of
rVSV-EBOV 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.
The rVSV-ZEBOV trial is
funded by WHO, with support from the Wellcome Trust, the UK Government through
the 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
Medecins Sans Frontieres.
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.
rVSV-ZEBOV 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.
