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With proper care, Ebola is less deadly, but prevention and cure are elusive

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CDC VIA AP

This undated file image made available by the CDC shows the Ebola virus.

It’s not a question of whether Ebola will return, but when.

Ebola expert Dr. Bruce Ribner makes the point repeatedly when discussing what could happen with the next outbreak of the deadly hemorrhagic fever virus.

Attention right now is concentrated on another viral threat, Zika, which unlike Ebola is transmitted through mosquitoes. But Ebola hasn’t disappeared since the outbreak of 2014. And the circumstances that led to its spread can appear again, unpredictably.

Moreover, effective preventives and therapies haven’t been yet invented, said Ribner, Emory University Hospital’s medical director of the Serious Communicable Diseases Unit. Ribner led preparations at Emory that made the hospital known as the best-prepared in the country for Ebola.

Emory’s hospital successfully treated a number of severely ill Ebola patients. That experience taught an important lesson: With proper supportive medical care, Ebola isn’t a death sentence.

While the experience was accompanied by panic, researchers like Ribner also obtained some much-desired funding. At the end of 2014, President Barack Obama and Congress agreed on $5.4 billion to treat and prevent Ebola, both in the United States and in West Africa, where the outbreak originated.

Among other things, that money is helping hospitals upgrade their preparedness to fight infectious diseases like Ebola. Hospitals such as that at Emory University represent the top tier.

And in West Africa, where the World Health Organization said on Jan. 14 that “all known chains of transmission have been stopped,” embers continue to flare.

On Jan. 21, a case was reported in Sierra Leone, one of the hardest-hit countries, the second in a week. (The first died). And Ebola survivors, of which there are now more than 10,000, can suffer from the debilitating aftereffects for many months, and even harbor the virus.

So the struggle to find better treatments, ideally resulting in a vaccine, is just as important as before.

Here’s a look at what the medical community has learned, and what unfinished business lies ahead:

Ebola is a member of a family of viruses called Filoviridae that can cause hemorrhagic fever. So while Ebola gets most of the attention, it’s not the only threat.

Ebola belongs to the genus Ebolavirus, consisting of five species: Zaire, Bundibugyo, Sudan, Reston (which doesn’t cause disease in people) and Tai Forest. Zaire is the species known as just Ebola, which caused the 2014 outbreak and others. Another worrisome virus, Marburg, belongs to a different genus, Marburgvirus. This viral diversity greatly complicates attempts to develop treatments.

However, a newly published study finds it is possible to develop an antibody-based treatment effective against multiple Ebolavirus infections.

The proposed treatment would be given post-exposure, to knock down the amount of virus in infected people, said Erica Ollmann Saphire, a study co-author who has been researching Ebola for years at the Scripps Research Institute. In that focus, Ollmann Saphire provides a research counterpart to Ribner’s clinical focus—although with Ebola, the research and clinical sides are tightly intertwined.

The study was published Jan. 21 in the journal Cell.

Antibody-based treatments have been extensively used for Ebola patients, such as an antibody “cocktail” being developed by San Diego’s Mapp Biopharmaceutical. The cocktail, called ZMapp, is not approved for human therapy. But good results from animal testing persuaded health professionals to use it on an emergency basis during the outbreak.

Ollmann Saphire and TSRI colleague Andrew Ward led a 2014 study that indicated a possible mechanism of action for ZMapp.

The new study, led by Andrew Flyak and James Crowe of Vanderbilt University in Nashville, finds that antibody protection could extend to other viruses with substantial differences in their genomes. Some of the antibodies they found neutralized not only Ebola Zaire, but also Ebola Sudan and Bundibugyo.

Antibody-based therapies are a good target for Ebola because their development path is well-known, Ollmann Saphire said, and is easier than developing small-molecule drugs.

“There’s a higher rate of approval for a number of different reasons,” Ollmann Saphire said. “But if you do that, you need a good antibody.”

Getting that good antibody often starts by screening human survivors of viral infections, but there weren’t many Ebola survivors from early outbreaks, she said. The first outbreak was identified in 1976.

“Now there’s a much bigger pool to work from,” she said. Scientists can understand what constitutes a really effective human response from someone who actually survived. And that’s what Crowe’s lab has done in the new paper.”

Once an effective antibody has been discovered, production by modern biotechnology methods is routine. A cell making the desired antibody is fused to an animal cell with a cancer called myeloma. This “hybridoma” replicates rapidly, and churns out exact copies, or clones, of the antibody, producing monoclonal antibodies.

Mapp went a different route at first, producing ZMapp in tobacco plants, but due to a production bottleneck later turned to hybridoma production, with the help of biotech giant Amgen.

As with the flu or HIV, finding an antibody that works against one strain is much easier than finding an antibody that works consistently even when the virus mutates or different strains spread.

However, the Cell paper said developing such universal antibody treatments for Ebola and related viruses “seems inevitable,” given recent progress made in finding potent broadly neutralizing antibodies against HIV, an even tougher target. Much of that work is being conducted at The Scripps Research Institute, which hosts a center for research on neutralizing antibodies against HIV.

The unpredictable nature of outbreaks of these hemorrhagic fevor viruses makes it highly desirable to have such a widely effective treatment, Ollmann Sapphire said.

“The last couple of years it was the Ebola virus species in West Africa, but it could just as easily been Sudan virus, Bundibugyo virus or Marbug virus,” she said.

Making antibodies is expensive, however. It’s cheaper to have people make the antibodies themselves, by giving them vaccines to stimulate production of effective antibodies. A properly designed vaccine will prevent infection, or at least greatly improve the immune system’s ability to defeat the infection.

On Jan. 20, $5 million was committed by a vaccine alliance called GAVI to develop an Ebola vaccine. The money will fund development of the vaccine by a subsidiary of Merck & Co. The vaccine contains a live, weakened form of Ebola, the same concept used in the widely distributed Sabin live virus polio vaccine.

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©2016 The San Diego Union-Tribune

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