Winnipeg, Manitoba (09/20/05)- A pair of test vaccines has proven
to be effective at protecting monkeys against the Ebola and Marburg
viruses.
Developed by researchers in Canada and the US, the vaccines represent a big
step forward in the quest to protect humans from these two deadly diseases.
Ebola
and Marburg are both hemorrhagic
fevers. Symptoms consist of sudden onset
of fever, muscle pain, tiredness, and sore throat, along with vomiting,
diarrhoea, and impaired kidney and liver function. Hemorrhagic
fevers affect
multiple organs in the body causing large amounts of both internal and external
bleeding. Outbreaks have mortality rates as high as 90%, and there are
no effective treatments for the diseases, Steven Jones, PhD, told Access
Excellence in an interview. He is head of immuno-pathology at the
Public Health Agency of Canada,
and lead author of a study recently published in Nature
Medicine describing the new vaccines. The diseases are spread by
direct contact with infected people or with infected bodily fluids.
Until recently, there have been several challenges when it came to developing
vaccines, one being the need for Level-4 containment -- laboratories that
are specially designed so there is no chance the disease will leak out of
the building. There are only about 17 of these special laboratories around
the world meaning only "a very small number of scientists could work
with them," Dr. Jones said. In recent years, researchers started working
with genetic components of the viruses which are not dangerous to handle.
Another challenge was that there are several different strains of Ebola,
each of which would require a different vaccine. "There are four distinct
species of Ebola. Their genome sequence is sufficiently different
that we can classify them as different species," Dr. Jones said. Those
species are Zaire-ebolavirus, Sudan-ebolavirus, Ivory Coast ebolavirus, and
Reston-ebolavirus. Marburg
strains are similar enough that one vaccine should do the trick.
The vaccines Dr. Jones and colleagues developed are live attenuated recombinant
vaccines. Live attenuated means a live virus is used, and recombinant means
new genetic components are introduced into the virus used in the vaccine.
But the virus used in the test vaccine is not from Ebola or Marburg, it is
from the vesticular stomatitis virus (VSV) which causes a disease in livestock
that causes symptoms similar to those of foot and mouth disease.
To create the vaccine, VSV is first disabled by removing the glycoprotein
from its surface. Researchers then insert the glycoprotein gene from either
Ebola or Marburg in its place. The foreign glycoprotein is expressed
on the surface of
the disabled
virus which the immune system of an injected person identifies as something
to protect against and creates immunity. In other words, the immune system
is tricked into thinking that the disabled or dummy virus is either Ebola
or Marburg and develops defenses against it.
The VSV serves as a delivery platform that presents, and carries around,
the Ebola or Marburg glycoprotein. "The new recombinant virus is capable
of growing and infecting cells, but it is not capable of causing disease
in animals," Dr. Jones said. The attenuated (inactivated) virus
actually enters healthy cells and grows within them, but because it is attenuated
does not cause disease. An advantage
of this
live virus approach, which is also used in some other vaccines, is that it
helps create rapid immunity against a disease. Other
types of vaccines take longer to trigger an immune response.
Two vaccines, one for Zaire-ebolavirus and one for Marburg virus (Musoke
strain), were tested on 12
macaque monkeys.
Six were injected with the vaccine against Ebola, and the other six were
give the Marburg vaccine. The health of the monkeys was monitored
to see whether there were adverse effects from the vaccines. There were none.
On day 29 after getting the vaccines, four of the Ebola-vaccinated monkeys
were exposed to the Ebola virus. As a control, the other two monkeys were
exposed to the Marburg virus instead. Of the monkeys that were vaccinated
against Marburg, four were exposed to the Marburg virus and two were exposed
to Ebola. Within three days, the control monkeys showed signs of illness
and were dead by day six. However, none of the monkeys exposed to the virus
they
were
vaccinated against got sick and all survived. The study showed that the Ebola
vaccine protected against Ebola, and the Marburg vaccine protected against
Marburg in the animals.
If the vaccine, in future studies, works against infection in people then
it could be used to protect medical workers who go to the places where there
are outbreaks. It could also potentially be used to protect against bioterrorism
attacks should Ebola or Marburg ever be used as biological weapons. "If there's
a vaccine for it, then it's not a good weapon," Dr. Jones said. Researchers
at other centers have made significant progress on a dead virus vaccine,
but it does not create immunity as quickly as a live virus vaccine would.
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