Read about a new, molecular view of the Ebola virus that could hold the key to countering this severe and often fatal disease.
Scientists in the Laboratory of Virology (LV) are developing vaccines that use an attenuated (weakened) vesicular stomatitis virus (VSV) to deliver a portion of an Ebola virus protein to the immune system. This is called a recombinant vector vaccine, in that it modifies the virus used as a vector, or carrier, to reach the immune system. The Ebola protein contained in the vaccine cannot cause disease, but it is enough to stimulate the immune system and teach it how to fight off Ebola virus in the case of future exposure.
LV scientists created a blended VSV-based vaccine by replacing a VSV protein with a glycoprotein (GP) from Ebola or Marburg. The experimental vaccine stimulated immune responses in nonhuman primates and offered complete protection from Ebola and Marburg infection at a dose 1,000 times lower than similar vaccines based on a different vector virus (the adenovirus vector.)
When given to animals after exposure to Ebola virus, the VSV-based vaccines could still prevent the animals from developing illness. This suggests that this form of vaccine could be used to treat disease after a person has been exposed. The LV group and collaborators are currently working on a second-generation VSV vector. Their goal is to get Food and Drug Administration approval for its use in humans as an emergency vaccine or treatment. Read more about research in the Laboratory of Virology.
Scientists in the Laboratory of Infectious Diseases (LID) are developing a nasal-spray vaccine for Ebola based on human parainfluenza virus type 3 (PIV-3). Because Ebola and PIV-3 enter the body in similar ways— through the mouth, eyes, or other mucosal tissue, LID scientists believe that PIV-3 is a good way to deliver the Ebola virus surface protein to the immune system. In guinea pigs and monkeys, the experimental vaccines induced a strong immune response. Read more about the Laboratory of Infectious Diseases.
Major areas of Ebola/Marburg vaccine research and development include: preclinical studies in nonhuman primates to identify lead vaccine candidates and immune correlates of protection against hemorrhagic fever viruses such as Ebola and Marburg; studies of the mechanism of vaccine-induced immune protection; and basic research to understand early virus-host interactions and virus strategies to circumvent host-mediated clearance mechanisms.
The Vaccine Research Center (VRC) is developing an Ebola vaccine containing two parts: a prime and a boost. The prime is a DNA vaccine containing a small piece of genetic material encoding surface proteins from Ebola-Zaire and Ebola-Sudan/Gulu. Later, the immune response is boosted with a second injection consisting of a viral vector that delivers the Ebola-Zaire surface protein. Ongoing studies in research using monkeys should guide further vaccine development. The first generation Ebola DNA and Ebola Ad5 vaccines were safe and well-tolerated, and subjects developed antigen specific humoral and cellular immune responses. A Phase I Marburg DNA vaccine candidate proved safe, well-tolerated, and immunogenic. Preliminary analysis of a Phase Ib clinical trial utilizing concomitant administration of the Ebola and Marburg vaccine candidates shows the products and vaccination strategy to be safe and well-tolerated.
The VRC has set the groundwork for rational vaccine development of a “Universal Ebola vaccine.” In order to identify possible cross-protective immunity against multiple Ebolavirus species, the VRC tested a DNA prime/rAd5 boost vaccine expressing viral proteins from the Zaire and Sudan strains in macaques followed by a lethal challenge with the new Bundibugyo strain and demonstrated that cross protection can be achieved by antigen-specific cellular immune responses in the absence of cross reactive antibodies.
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Last Updated November 17, 2010
Last Reviewed May 14, 2010