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Test Vaccines Protect Macaques Against Marburg, Ebola

By Pippa Wysong, Access Excellence

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.

ebolphaclabsept05Ebola 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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