Scripps Research Team Finds A Weak Spot On Deadly Ebolavirus

Scientists from The Scripps Research Institute and the US Army's Medical Research Institute of Infectious Diseases have isolated and analyzed an antibody that neutralizes Sudan virus, a major species of ebolavirus and one of the most dangerous human pathogens. "We suspect that we've found a key spot for neutralizing ebolaviruses," said Scripps Research Associate Professor Erica Ollmann Saphire, who led the study with US Army virologist John M. Dye.

The new findings, which were reported November 20, 2011, in an advance online edition of Nature Structural & Molecular Biology, show the antibody attaches to Sudan virus in a way that links two segments of its coat protein, reducing their freedom of movement and severely hindering the virus's ability to infect cells. The protein-linking strategy appears to be the same as that used by a previously discovered neutralizing antibody against the best-known ebolavirus species, Ebola-Zaire. The new study suggests that this may be the best way for vaccines and antibody-based therapies to stop ebolaviruses.

Deadly Outbreaks

Ebolaviruses first drew the attention of the medical world with simultaneous deadly outbreaks in 1976 in the nations of Sudan and Zaire (currently known as the Democratic Republic of the Congo). These two outbreaks were caused by the two major viruses: Ebola-Sudan and Ebola-Zaire, and early field studies showed that sera from patients that survived one virus could not help patients infected with the other. . Both viruses persist in animal hosts-probably bats-and when they spread to humans, typically cause severe hemorrhagic fevers, killing up to 90 percent of people they sicken. Although not as contagious as influenza or measles, ebolaviruses can be transmitted in bodily fluids including exhaled airborne droplets, and scientists who study these viruses are generally required to use special "Biosafety Level 4" facilities. The US government regards the ebolaviruses as a potential bioterror threat.

Ebolavirus researchers hope to develop a vaccine that could be used to protect health workers and others in the vicinity of ebolavirus outbreaks, as well as an antibody-based immunotherapy that could help infected people survive. However, these tasks are complicated by the fact that there are now five recognized species of ebolavirus: Ebola-Zaire, also known simply as Ebola virus; Taï Forest virus; Reston virus; Bundibugyo virus; and Sudan virus.

"These species differ enough from each other that neutralizing antibodies to one don't protect against the rest," said Ollmann Saphire. "Sudan virus is a particular concern because it has caused about half of the ebolavirus outbreaks so far, including the largest outbreak yet recorded."

Uncovering the Body's Natural Protection

US government researchers recently demonstrated that an experimental vaccine containing proteins from Ebola and Sudan viruses provides monkeys with some protection against those viruses. But precisely how the vaccine works is unclear, and it has never been tested in humans. Moreover, until now no laboratory has isolated a neutralizing antibody against Sudan virus.