Protection against Ebola, one of the world’s deadliest viruses, can be achieved by a vaccine produced in insect cells, raising prospects for developing an effective vaccine for humans, say scientists at the Southwest Foundation for Biomedical Research (SFBR) in San Antonio.
“The findings are significant in that the vaccine is not only extremely safe and effective, but it is also produced by a method already established in the pharmaceutical industry,” says SFBR’s Ricardo Carrion, Ph.D., one of the primary authors of the study. “The ability to produce the vaccine efficiently is attractive in that production can be scaled up quickly in the case of an emergency and doses can be produced economically.”
The new study was published in the January 2009 issue of the journal Virology, and was supported by the National Institutes of Health. Jean Patterson, Ph.D., also of SFBR, participated in the research.
Ebola viruses, which cause severe bleeding and a high fatality rate in up to 90 percent of patients, have no effective treatment or vaccine. Since its first identification in Africa in 1987, Ebola outbreaks have caused some 1,800 human infections and 1,300 deaths. Outbreaks have become increasingly frequent in recent years, and are likely to be caused by contact with infected animals followed by spread among humans through close person-to-person contacts. Ebola viruses cause acute infection in humans, usually within four to 10 days. Symptoms include headache, chill, muscle pain, followed by weight loss, delirium shock, massive bleeding and organ failure leading to death in two to three weeks.
Ebola viruses are considered a dangerous threat to public health because of their high fatality rate, ability to transmit person-to-person, and low lethal infectious dose. Moreover, their potential to be developed into biological weapons causes grave concern for their use as a bioterrorism agent. While some vaccines show protection in non-human primate studies, the strategies used may not be uniformly effective in the general human population due to pre-existing immunity to the virus-based vaccines.
In the new study, a vaccine using Ebola virus-like particles (VLPs) was produced in insect cells using traditional bio-engineering techniques and injected into laboratory mice. A VLP vaccine is based upon proteins produced in the laboratory that assemble into a particle that, to the human immune system, looks like the virus but cannot cause disease.
Two high-dose VLP immunizations produced a high level immune response in mice. And when the twice-immunized mice were given a lethal dose of Ebola virus, they were completely protected from the disease. In contrast, mice that were not immunized had a very low immune system response and became infected. In another experiment, a three low-dose VLP immunization effectively boosted immune system response in mice and protected them against the Ebola virus. This finding is important because it demonstrates that since the vaccine produces immunization in dilute quantities, many more vaccine doses can be generated compared with a poorly immunogenic vaccine.
VLPs are attractive candidates for vaccine development because they lack viral genomic material and thus are not infectious, are safe for broad application, and can be administered repeatedly to vaccinated individuals to boost immune responses.
The findings will be validated in additional animal systems. The vaccine will then undergo FDA safety and efficacy testing prior to use in humans in potentially five years.
Collaborators on the study included Richard Compans, Ph.D., and Chinglai Yang, Ph.D., of the Emory University School of Medicine in Atlanta.
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