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New Approaches Speed Ebola Vaccine Development

By Nancy Touchette

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Scanning electron micrograph of the Ebola virus.
The first clinical trial to test an Ebola vaccine in humans is halfway complete, and researchers are seeking additional volunteers to begin the final phase. At the same time, researchers are pursuing two very different new vaccines that may prove more useful in outbreak situations.

The clinical trial, conducted by the U.S. National Institute of Allergy and Infectious Diseases (NIAID), is assessing the safety and immune response of different doses of a DNA vaccine. Fourteen volunteers have enrolled so far. An additional seven to ten subjects are needed to complete the study.

Gary Nabel, of NAID’s Vaccine Research Center, who is leading the research, predicts that if the DNA vaccine currently being tested in humans proves safe, it could be available in a few years as part of a long-term preventive vaccine to protect against infection in health care workers, military personnel, and primary responders to a possible bioterrorism attack.

The DNA vaccine, which contains three genes from the Ebola virus, must be given multiple times over several months to confer protection against Ebola hemorrhagic fever—a severe, often-fatal disease that afflicts humans and apes.

For this reason, researchers are pursuing other strategies to develop a vaccine that could be used in an Ebola outbreak.

Usually the term “vaccine” refers to a preparation that elicits immunity, so that the recipient is protected if exposure occurs. In the case of Ebola, which occurs rarely, it is unlikely that everyone would be vaccinated even if such a vaccine existed. Health workers need to be immune themselves, and they also need a vaccine that they can administer either before or possibly in the early stages of an outbreak.

Now, even as trials for the current vaccine proceed, researchers are testing two new “accelerated” vaccines in animals. The vaccines use common viruses—unrelated to Ebola—to deliver genes from the Ebola virus to the host. The Ebola genes cannot cause disease in the host, but can trigger an immune response that will protect those who are exposed to the real thing.

“Accelerated” vaccine protects monkeys

Last summer, NIAID researchers described an “accelerated” vaccine that protects monkeys from Ebola infection a month after receiving a single dose.

The accelerated NIAID vaccine uses a defective adenovirus, which normally causes a respiratory infection in humans. The researchers removed a gene that the adenovirus needs to replicate and inserted an Ebola gene. Nabel says crippling the adenovirus is important so that it doesn’t cause disease in humans.

“Live” pox-like virus altered to protect mice from Ebola

Last week at the American Society for Microbiology’s Biodefense Meeting in Baltimore, Maryland, researchers from Health Canada in Winnipeg reported that a potential new vaccine protects mice even when given 30 minutes after direct exposure to the virus.

A successful mouse vaccine does not always work in monkeys or humans, but Heinz Feldmann, who led the Canadian study, says that preliminary tests indicate that the vaccine can also prevent Ebola infection in monkeys. However, it is not yet known whether the vaccine can protect monkeys when given close to or immediately following exposure to the virus.

The Canadian vaccine differs from the accelerated NIAID vaccine in that it uses a live, replicating virus called vesicular stomatitis virus, which causes a pox-like disease in cows. The virus can infect humans, but does not usually cause disease. The virus continually produces the protein needed to trigger an immune response against Ebola, so that repeated dosing is not necessary.

When a single dose is delivered orally or intranasally to mice, all animals are protected from Ebola for as long as nine months with no additional boosters needed. When given 30 minutes after exposure to Ebola virus, 80 percent of the animals survive.

“The advantage of using a replicating virus is that you get a much better and more potent immune response,” says Feldmann. “It’s kind of a natural boost effect which means you can avoid a longer immunization schedule. This could be advantageous in an outbreak situation.”

Nabel urges caution about using live replicating viruses to develop vaccines, however.

“There is concern over releasing an uncontrolled animal pathogen into the environment,” says Nabel. “But there may be a way to make it more safe.”

Nabel says it is important to pursue all approaches nevertheless, as researchers strive to develop the ideal vaccine.

The newer accelerated vaccines might be useful as boosters to a preventive vaccine or to protect a population during an Ebola outbreak. These vaccines face daunting regulatory hurdles and are many years away from use in humans.

Sullivan, N.J. et al. Accelerated vaccination for Ebola virus hemorraghic fever in non-human primates. Nature 424, 681-684 (August 2003).

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