Trial confirms Ebola vaccine candidate safe

Trial confirms Ebola vaccine candidate safe

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Two experimental DNA vaccines to prevent Ebola virus and the closely
related Marburg virus are safe, and generated a similar immune
response in healthy Ugandan adults as reported in healthy US adults
earlier this year. The findings, from the first trial of filovirus vaccines
in Africa, are published in The Lancet.

“This is the first study to show comparable safety and immune
response of an experimental Ebola vaccine in an African population,”
says lead author Dr Julie Ledgerwood from the National Institutes of
Allergy and Infectious Diseases at the National Institutes of Health,
USA. “This is particularly encouraging because those at greatest risk
of Ebola live primarily in Africa, and diminished vaccine protection in
African populations has been seen for other diseases.”

Scientists from the NIAID developed the DNA vaccines that code for
Ebola virus proteins from the Zaire and Sudan strains and the Marburg
virus protein. The vaccines contain the construction plans for the
proteins on the outer surface of the virus. Immune responses against
these proteins have shown to be highly protective in non-human
primate models.

In this phase 1 trial, the Makerere University Walter Reed Program
enrolled 108 healthy adults aged between 18 and 50 from Kampala,
Uganda between November, 2009 and April, 2010. Each volunteer was
randomly assigned to receive an intramuscular injection of either the
Ebola vaccine (30 volunteers), Marburg vaccine (30), both vaccines
(30), or placebo (18) at the start of the study, and again 4 weeks and
8 weeks later.

The vaccines given separately and together were safe and stimulated
an immune response in the form of neutralising antibodies and T-cells
against the virus proteins. Four weeks after the third injection, just
over half of the volunteers (57%; 17 of 30) had an antibody response
to the Ebola Zaire protein as did 14 of 30 participants who received
both the Ebola and Marburg vaccines. However, the antibodies were
not long-lasting and returned to undetectable levels within 11 months
of vaccination.

Both DNA vaccines were well tolerated in Ugandan adults with similar
numbers of local and systemic reactions reported in all groups. Only
one serious adverse event (neutropenia; low white blood cell count)
was reported in a Marburg vaccine only recipient, but was not thought
to be vaccine related.

According to Dr Ledgerwood, “These findings have already formed the
basis of a more potent vaccine, delivered using a harmless
chimpanzee cold virus, which is undergoing trials in the USA, UK, Mali,
and Uganda in response to the ongoing Ebola virus outbreak.”

Writing in a linked Comment, Dr Saranya Sridhar from the Jenner
Institute at the University of Oxford in the UK says, “[This] study
deserves to be the focal point around which the broader question of
vaccine development, particularly for Africa, must be addressed. With
the uncharitable benefit of hindsight in view of the evolving 2014
Ebola outbreak, we must ask ourselves whether a filovirus vaccine
should have been in more advanced clinical development.

The international response to the present Ebola outbreak is an exemplar of the speed and purpose with which clinical vaccine development can progress and has set the benchmark against which future vaccine development must be judged. This study is the first step on the aspirational road towards the deployment of filovirus vaccines in Africa and must serve to shake the metaphorical cobwebs that can stall our advance towards this destination.”