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Success in primates sparks hope for Marburg vaccine

June 5, 2005 By Emma Marris This article courtesy of Nature News.

Live inoculations join the fight against fatal fevers.

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An epidemic of Marburg disease continues to ravage Angola, with 335 dead as of 26 May. But a glimmer of hope may be provided by a vaccine for the fever that has recently proven its efficacy in primates.

The vaccine team has also made progress with a jab against the related Ebola virus, which has killed hundreds in Africa since the 1970s.

There are no treatments for either of these viral fevers, which cause blood vessels to deteriorate and are often fatal. The newly developed Marburg jab is the first to beat this infection in primates.

The vaccines are made from live, deactivated viruses that have been modified to confer immunity to one disease or the other. They may prove more effective than an Ebola vaccine currently being tested on humans that uses dead viruses to provoke an immune response. But some scientists caution that the live virus comes with a small risk: it might mutate back to a virulent form and cause disease.

Live aid

The group testing the live vaccines, headed by Steven Jones of the Public Health Agency of Canada, built their jabs around a rare livestock virus that causes a disease known as vesicular stomatitis.

After being rendered harmless through gene shuffling, the viruses were covered with distinctive proteins that the human body uses to recognize and marshal defences against either Marburg or Ebola.

Six macaques were given a jab against Marburg disease; four were then infected with Marburg virus and two were infected with Ebola. The four infected with Marburg survived; the others died within ten days. The same procedure was used for jabs against Ebola disease; again, the four that got the right shots survived; the other two died. The results are published in this month's Nature Medicine1.

Natural defence

The vaccine that uses dead viruses was developed by Gary Nabel's lab at the National Institutes of Health in Bethesda, Maryland. It is built around an adenovirus, a category of virus that includes the culprit behind the common cold. In 2000, Nabel's team showed that it protects macaques from Ebola2.

However, many people already have antibodies to natural adenoviruses, which may limit their immune response and lower this vaccine's effectiveness. In contrast, very few people carry immunity to vesicular stomatitis.

Jones's team points out that the live vaccine is in some ways easier to produce, and requires a smaller dose. "You can make a little go a long way," says co-author Thomas Geisbert, who has been working on Ebola at the United States Army Medical Research Institute of Infectious Diseases in Fort Detrick, Maryland, since the late 1980s. But Nabel is concerned that it will revert to a dangerous form or hop over into cattle.

On all fronts

Both teams hope their vaccines will be on the market in three to seven years. The jabs could be used earlier than that, however, if they prove useful in preliminary studies and an outbreak demands their use on compassionate grounds.

The teams emphasize that all possible strategies should be pursued to ensure that the diseases are tackled effectively. Geisbert says he is anxious for a vaccine to be approved, so he and other researchers exposed in the field can take it.

"I would sleep a lot better at night if I knew that the people who worked for me, the postdocs and the caretakers, were vaccinated," says Geisbert.

References

  1. Jones S., et al. Nature Medicine, 11. Published online. doi:10.1038/nm1258 (2005).
  2. Sullivan N., Sanchez A., Rollin P., Yang Z. & Nabel G. et al. Nature, 408. 605 - 609 (2000).

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