Rabies and ebola combination vaccine in the pipeline – silencing genes controlling aggression?

Rabies and ebola combination vaccine in the pipeline – silencing genes controlling aggression?

August 16, 2014
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In his novel “The Cobra Event”, Richard Preston describes a bioengineered virus that silences genes which control aggression.

The people infected become rabid, attacking themselves and others, and so are transformed into bioweapons who spread the disease, every eugenicist’s dream.

November 2, 1997

http://www.nytimes.com/books/97/11/02/reviews/971102.02harrist.html

A Hotter Zone The disease in Richard Preston’s novel makes people’s brains melt in their skulls.

By COLIN HARRISON

THE COBRA EVENT
By Richard Preston.
404 pp. New York:
Random House. $25.95.

Nobody, it seems safe to say, wants to have his or her face slide off like overcooked oatmeal. This was something we were all supposed to be worrying about — remember? Three years ago, Richard Preston’s best seller, ”The Hot Zone,” appeared, a nonfiction reconstruction of an outbreak of Ebola virus in a Virginia monkey quarantine installation, and, like a germ dropped into a ready petri dish, Ebola bloomed in the cultural consciousness. Although the outbreak in Virginia resulted in exactly zero human cases, the idea of an exotic virus that savages its victims effectively replicated itself in newspaper stories, copycat novels, television fright-fests and at least one movie, ”Outbreak.” The happy frenzy showcased our mass media at their recombinantly contagious worst: it was the first time that everyone knew about a disease that nobody had. It was the first time that a virus was famous for being famous.

Preston is back, with another disease, and another book. ”The Hot Zone,” a work of journalism that relied on the techniques of thriller fiction, has given way to ”The Cobra Event,” a thriller that relies on the solemn tones of journalism. Readers hoping for more passages detailing the gruesome goopiness of human flesh won’t go away unsplattered.

”The Cobra Event” begins with a cluster of New Yorkers falling victim to an unidentified malady that causes them to writhe miserably and do nasty things before they expire. As we will learn, their brains are melting inside their skulls. Enter Alice Austen, M.D., an epidemiologist at the Centers for Disease Control, 29, ”slender,” with ”wavy auburn hair,” a woman who has ”had her lovers, including a man who wanted to marry her.” That’s about all that we’ll ever get to know about Alice, except that she is one heck of an epidemiologist. Yes, Alice has the disease-sleuthing magic. She will join up with other Federal researchers as they identify one victim after another and diagnose the killer disease.

But readers planning on light airplane reading had better buckle up for pedantic weather. The story of the Government’s frantic high-tech effort to beat the virus is interwoven with passages and chapters of explanatory exposition on the history, science and politics of germ warfare. A few phrases from Preston’s introduction suggest his intentions: ”For many years, the scientific community told itself and the public that biological weapons were not much of a problem. . . . Experts are reluctant to talk too freely. . . . The public simply must be told . . . the lessons of history.”

Preston’s real-world agenda apparently even requires ”The Cobra Event” to have a glossary. Yes, one should not judge a book by its glossary. But here, self-importantly, are entries for such terms as cloning, gene, pathologist, swab (”Looks like a long Q-Tip”) and virus. It’s as if Preston were worried that the reader will miss the deeply researched message of the book, instead simply succumbing to the wish to read a swift-paced intrigue. Sermons, he has forgotten, are for Sundays.

When Preston lets his scenes run, however, they are enormously entertaining. His prose is strongest when describing the physical world, whether it is the way a low-flying jet ripples the ocean or a pathologist cuts open a skull: ”The scalp was now reversed and hanging down from her bare forehead bone, covering her eyes, so the wet, glistening red inner layer of the scalp was on the outside, like a hat pulled down low.”

Preston is equally adept at dramatizing contagion. Although the plot requires a bad guy — in this case a genetic engineering wizard who calls himself Archimedes — the real villain here is the madman’s ”brainpox,” which includes a pinch of an obscure moth virus, smallpox and Lesch-Nyhan disease, a rare birth disorder. The brainpox requires otherwise decorous human beings to gobble their bottom lips, bite off their own fingers, and in extreme cases to ”enucleate” themselves (remove one’s own eyeball) spontaneously. The early symptoms of the brainpox are the same as those of a rhinovirus (glossary: ”the common cold virus”), and while reading I noticed that my nose was a bit leaky and thus couldn’t help worrying.

Like any respectable archfiend, the brainpox has supporting characters — an evil Russian female scientist, a weak-principled American bio-company entrepreneur — and the pursuit of the virus makes for an agreeably far-flung story. Preston ably connects a Vietnam War-era germ warfare test a thousand miles southwest of Hawaii, a contemporary United Nations inspection of an Iraqi biological weapons factory and a woman peddling junk on the streets of Manhattan.

But in so doing he finally pushes ”The Cobra Event” onto a rather conventional track. How many conclusions to thrillers include F.B.I. helicopters, ninja assault soldiers, a chase through a subway, shots ringing out in the darkness and a confrontation between the intrepid heroine and the bad guy? The answer: Who knows, but it’s a lot. The better question is whether Preston, or any writer, can really accomplish his stated goal using such tired plot riggings. Perhaps apocalyptic warnings require new plot forms, not just glossaries. Then again, would readers care? Gorged on F.B.I. helicopters, would they, could they, try something new?

Colin Harrison is the deputy editor of Harper’s Magazine. His most recent novel is ”Manhattan Nocturne.”

http://www.nytimes.com/books/97/11/02/reviews/971102.02harrist.html

Interestingly, researchers at Thomas Jefferson University in Philadelphia have produced an Ebola vaccine that piggybacks on the established rabies virus, raising the question of whether bioweapons scientists are planning to introduce a virus like the one described in “The Cobra Event.”

“Matthias Schnell, director of the Jefferson Vaccine Center, believes that the combination rabies/Ebola vaccine his team is working on likely has the best chance to be disseminated prior to an outbreak,” reports CBS.

By Dennis ThompsonHealthDayApril 14, 2014, 1:35 PM
http://www.cbsnews.com/news/as-ebola-outbreak-spreads-vaccine-remains-years-away/

As Ebola outbreak spreads, vaccine remains years away

In this photo provided by MSF, Medecins Sans Frontieres (Doctors without Borders), taken on Friday, March 28, 2014, healthcare workers prepare isolation and treatment areas for Ebola hemorrhagic fever in Gueckedou, Guinea. AP Photo/Kjell Gunnar Beraas, MSF

As a major outbreak of deadly Ebola virus spreads through the West African nations of Guinea and Liberia, public health officials are struggling to contain the horror-movie pathogen before it slips into neighboring countries.

They must do so without the aid of any vaccines to prevent Ebola’s spread or medicines to treat Ebola infections. None currently exists.

But scientists say they are beginning to close in on ways to stop the virus. Several promising vaccines and medications are under development, although all are still years from availability, said Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases (NIAID).

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Ebola outbreak strikes West Africa
Currently, the best treatment for Ebola involves providing fluid to the patient to replace the bleeding that occurs from all orifices as the hemorrhagic fever destroys the body from within.

“If you have a medical facility to give you blood or plasma or fluid, you’re not specifically attacking the Ebola, but you’re giving the patient a better chance of surviving,” Fauci explained. “Some people who have the best medical care still die, and there are some people with no care who survive. But you have the best chance if you have medical care.”

As of late last week, the number of suspected cases in Guinea had swelled to 158, with 101 deaths, according to the World Health Organization. There are 25 reported cases in nearby Liberia, including 12 deaths.

Most deaths have occurred in the southeastern Guinea city of Guekedou, which lies near the borders of Sierra Leone and Liberia. Suspected cases have been reported in Sierra Leone, Mali and Ghana, but none has been confirmed.

Ebola’s average death rate is about 70 percent, but can range between 20 percent and 90 percent depending on the strain, Fauci said.

The most promising efforts to develop an Ebola vaccine involve genetic splicing, Fauci said. In this line of research, NIAID investigators and several pharmaceutical firms are pursuing separate research that would insert part of Ebola’s genetics into an existing vaccine-ready virus.

This strategy, called a viral vector, takes advantage of the ability of viruses to efficiently infect cells.

Instead of delivering a payload of illness, these modified, harmless viruses would deliver a nonthreatening piece of Ebola’s genetics in hopes of triggering an immune response that would create antibodies to protect against future Ebola infection.

“You take another virus and you take the particular gene of the Ebola virus for which you want to prompt immunity, and you insert that gene into the virus,” Fauci explained.

Researchers at Thomas Jefferson University in Philadelphia are spearheading another research effort along similar lines. They have produced an Ebola vaccine that piggybacks on the established rabies virus vaccine, and the new combination has successfully immunized mice and primates in lab tests against both rabies and Ebola.

“I think we’ve demonstrated it is efficient in animal models, and now we have to produce a vaccine that would be appropriate for humans,” said Matthias Schnell, director of the Jefferson Vaccine Center.

This vaccine actually uses a surface protein taken from Ebola, rather than pieces of its genetic material, to create the immune response, Fauci said.

All of these vaccines are nowhere near human trials, however, Schnell and Fauci said. The most advanced efforts are currently undergoing pre-clinical evaluation, and are still years away from phase I trials that would determine whether the vaccines would be safe in humans and provoke the necessary immune response.

“We now have a grant from the [U.S. National Institutes of Health] for five years to develop clinical material,” Schnell said. “Our first clinical trial can be performed in two to three years, hopefully.”

Also under development are therapies that could help people who have contracted Ebola or who are likely to come into contact with it.

These therapies mainly involve the creation in the lab of antibodies against Ebola. The antibodies — called monoclonal antibodies — are designed to specifically target the Ebola virus.

The Public Health Agency of Canada is preparing clinical studies in humans for a monoclonal antibody its researchers have developed, Fauci said. A private company, Mapp Biopharmaceutical of San Diego, also has shown encouraging results in primates using a cocktail of monoclonal antibodies.

Another company, BioCryst Pharmaceuticals, of Durham, N.C., has developed an antiviral drug called BCX4430 that could be used to treat people infected with Ebola. “They’re already looking at nonhuman primate studies to see if they can protect them,” Fauci said.

There’s one problem with all these medical research efforts, however: researchers likely will have to wait for a future Ebola outbreak to test any vaccine or treatment.

Ebola is a rare disease and its outbreaks are unpredictable, making widespread vaccination an unfeasible proposition, Fauci said.

Schnell believes that the combination rabies/Ebola vaccine his team is working on likely has the best chance to be disseminated prior to an outbreak.

“Rabies is a huge problem in Africa, so with a double vaccine you would have a strong reason to vaccinate,” he said. “But it’s not really easy to predict where Ebola will erupt, and where mass vaccinations will be needed.”

This time the Ebola outbreak hit a major city, Schnell said, which is a real concern that further emphasizes the need for a vaccine.

It also raises concerns that Ebola could spread to the United States or other countries via air travel, but both Schnell and Fauci said that scenario is unlikely.

Unlike respiratory viruses, which spread via coughing, Ebola spreads “when people come into direct contact with the bodily fluids of someone who is in dire straits,” Fauci said. “It is not the kind of virus that is transmitted through casual contact with someone who is well.”

That’s why family, doctors, morticians and clergy are more likely to come down with Ebola during an outbreak — they are the ones tending to the ill. And it is unlikely that someone who is ill enough to be bleeding from their orifices will be able to make it onto an airplane, the experts said.