A devastating tropical virus that has no cure can be ambushed by vaccination a day or two after exposure, tests in monkeys show. The findings suggest that African villagers, health officials and laboratory workers who come into contact with the deadly Marburg virus will someday have recourse to fend it off. The report appears in the July Emerging Infectious Diseases.
Marburg virus is related to Ebola virus. Both cause hemorrhagic fevers — in severe cases leading to shock, delirium and organ failure — and have high mortality rates in humans. This week, the World Health Organization reported five cases of hemorrhagic fever, three of them fatal, among hunters in the Republic of Congo’s remote north.
In recent decades cases of Marburg virus have shown up in Uganda, Zimbabwe, the Democratic Republic of the Congo, Kenya, and Angola, sometimes spreading to other countries via infected travelers.
Earlier research showed that monkeys exposed to Marburg virus and vaccinated within an hour survived (SN: 5/6/06, p. 277). In the new study, six rhesus macaques were exposed to the virus and not vaccinated until 24 hours had passed, a strategy designed to mimic situations in which people are exposed, says study coauthor Heinz Feldmann, a virologist at the Rocky Mountain Laboratories of the National Institute of Allergy and Infectious Diseases in Hamilton, Mont.
Five of the infected animals fended off the disease; one died. Of six other monkeys similarly exposed but not vaccinated until 48 hours had passed, two survived and four died.
Clinical reports of past Marburg virus outbreaks suggest that people can be exposed longer to the virus than monkeys before showing symptoms. Feldmann says that the window of opportunity for vaccination after exposure might therefore be greater. Also the animals in these tests were given a high dose of the virus, possibly higher than the levels people might be exposed to in an outbreak.
“I think this would have tremendous value in public health workers and families affected by Marburg virus outbreaks,” says Daniel Bausch, an infectious disease physician at the Tulane University School of Public Health and Tropical Medicine in New Orleans. The problem will be to reach people in time, as most people don’t know when they have been exposed during an outbreak. Even so, Bausch says a vaccine could be an “extremely important tool” in those situations.
The vaccine, which is delivered in a single injection, contains a harmless livestock virus with a single surface glycoprotein from the Marburg virus. The resulting live, attenuated combination virus doesn’t cause disease in primates, but it does awaken the immune system, which rapidly gins up an army of cells and proteins to fight the Marburg infection. Feldmann says the vaccine also seems to compete with the lethal virus for access to important target cells, including dendritic cells — immune cells that are pivotal in engineering retaliation against a foreign pathogen.
This competition to enter dendritic cells may prevent the Marburg virus from infecting these cells, Feldmann says. Dendritic cells are immune orchestrators, presenting foreign compounds to other immune cells for inspection and also secreting proteins such as cytokines that serve as biological bread crumbs, leaving a trail that other immune warriors can follow to attack cells infected by the lethal virus.
Preserving dendritic cell function may buy time for the immune system — over several days — to produce T cells and antibodies that ultimately wipe out the Marburg virus, he says.
Vaccine tests in monkeys exposed to Ebola virus also look promising (SN: 7/16/05, p. 45). But there will never be a true trial of these vaccines in people because it would be ethically unacceptable to expose an individual to live Marburg or Ebola virus, even with the vaccine. Nevertheless, Feldmann hopes that funding can be provided to induce the vaccine industry to manufacture batches of each vaccine to have ready for the next outbreak and for lab personnel working with these viruses.
Hemorrhagic fever outbreaks crop up without warning. Evidence suggests the viruses are carried by fruit bats (SN: 12/24/05, p. 416) and may exist in other animals. Ebola can infect gorillas (SN: 12/9/06, p. 371) and chimpanzees; Marburg was originally known as “green monkey disease.”