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Inside the lab: the race to create an Ebola vaccine

Protein Sciences Corp. joined a handful of other biotechnology companies racing toward a vaccine or treatment of Ebola, which has taken more than 5,600 lives in West Africa.

Protein Sciences scientist Keyang Wang works in the company's labratory in Meriden, Conn. The company is working to create a vaccine for the Ebola virus. (Michael McAndrews/Hartford Courant/TNS)
Protein Sciences scientist Keyang Wang works in the company's labratory in Meriden, Conn. The company is working to create a vaccine for the Ebola virus. (Michael McAndrews/Hartford Courant/TNS)Read more


MERIDEN, Conn. — Rick Chubet paces from machine to machine inside a clean, white lab at Protein Sciences.

The vaccine scientist pulls up to a monitor displaying fresh results from a test. Two lines, one blue, one red, cut across a graph. He walks to another area, where more data waits.

"This is good news," he says, pointing to a cluster of blue lines that tells him he is zeroing in on the protein he wants.

Tasks and projects at Protein Sciences differ depending on the day. Sometimes, Chubet wakes up at his home in Middletown, drives to Meriden and launches into work on a vaccine for influenza, an illness that still kills more than 30,000 in the United States each year despite the widespread use of vaccines. Other days, it might be rabies, which results in a similar number of deaths worldwide, mostly in Africa and Asia.

This early November morning, the target is Ebola.

Protein Sciences Corp., a pharmaceutical company of 130 employees, jump-started work on the virus in July after discussions with officials from the National Institutes of Health and the U.S. Biomedical Advanced Research and Development Authority. In so doing, it joined a handful of other biotechnology companies racing toward a vaccine or treatment of Ebola, which has taken more than 5,600 lives in West Africa.

Protein Sciences had in cold storage a half-completed vaccine from 2010, when U.S. public health officials pushed Ebola research. The genetic work was done, leaving just the manufacturing and Chubet's job: purifying the vaccine to its essence.

"I have two weeks to figure it out, and we are damn close," he says.


Chubet, 54, stands at a workstation, wearing a white lab coat over blue jeans and a gray pullover.

He delves into the finer points of molecular biology and the behavior of viruses as if the world can keep up with him and see the scientific methods as clearly as he does. A man partly responsible for an innumerable number of people being stuck in the arm, Chubet says he avoids needles whenever possible.

Protein Sciences is becoming known for its influenza vaccine, Flublok, and in recent months landed a large distribution deal for the drug as well as an important decision from the U.S. Food and Drug Administration to extend its approval to older people. The company spent about two decades and more than $100 million on Flublok.

Technical differences aside, the production of the flu vaccine mirrors the process Chubet and his team are following as they rush to get a vaccine for Ebola to next-stage clinical studies.

Chubet needs to separate the exact vaccine proteins from a milkshake-like soup of broken cells, waste protein, shattered DNA, and other particles that the company's manufacturing division sends him.

His lab equipment works as a type of sieve that, when loaded with the right filters that strain out unwanted particles, can separate out the vaccine protein, called a glycoprotein. The plan for Chubet is to send doses of the purified protein to the NIH by early December.

In the middle of a four-week push on the vaccine, Chubet seems content with his progress. "We have done pretty well for just two weeks. For flu, we worked on it for years."

But Ebola, Chubet is finding, is a complex and fragile virus.

And while Chubet battles in the lab, the possibility of a clinically tested Ebola vaccine faces more than just technical hurdles.

One, Protein Sciences is a private company and limited in how much of its own capital it will put toward this early work. Two, there is no formal market for an Ebola vaccine, so any feasible solution would require a governmental partnership or a deal with a pharmaceutical company that could find public financing.

Also, Protein Sciences is not the only pharmaceutical company with an iron in the fire. At least half a dozen other vaccines or treatments are in various development stages, including one backed by British drug giant GlaxoSmithKline and another recently bought by Merck.


For Manon Cox, chief executive of Protein Sciences, the real worry is more than competition from pharmaceutical giants. The largest threat is that the now-strong push for a vaccine could fade.

She sees support for an Ebola vaccine as fragile and fears that the public will misunderstand signs of improvement in Western Africa as success. If that happens, pressure to conquer the outbreak could wash away.

"The complacency turns up," she says. "The virus is still out there. And it might come back much harder."

Cox studied business and microbiology in the Netherlands before joining Protein Sciences in 1998. She saw funding disappear from an Ebola vaccine project the company worked on in 2010.

Protein Sciences also produced a bird-flu vaccine in eight weeks at the request of the public health officials in the United States. But then the need for that vaccine vanished.

The Ebola virus is believed to live in African fruit bats. From there it is thought to jump straight to humans or mammals that are hunted for meat, known as bushmeat.

The current outbreak is West Africa's first, something that researchers have slowly begun to resolve. Researchers at Virginia Tech, Columbia University and elsewhere found that humans pushing into formerly forested areas where the virus lives in animals helped cause the outbreak.

"These environmental changes in the outbreak region may provide the opportunity for direct exposure to infected bats, potentially creating transmission pathways that do not rely on exposure to bushmeat," researchers say.

Greater urban populations and increased mobility also increased the spread of the disease, the researchers say in the paper, conditionally accepted by the journal Public Library of Science's Neglected Tropical Diseases.

The world lacks an Ebola vaccine mainly because of the way the virus has behaved in the past. Seventeen outbreaks since 2000 have come and gone, most resulting in only a small number of cases in rural areas. The short period from emergence to disappearance leaves little time for the clinical work to approve a vaccine before the demand fades.

Researchers at Yale, in the Annals of Internal Medicine, say the time to deploy vaccines is now, and argued that vaccines should be able to reach approval from animal studies and other diagnostics.

"The relentless epidemiologic trajectory and geographic dissemination represent a public health crisis that shows no signs of diminishing under current efforts," researchers at the Yale School of Public Health wrote.

They also recommended vaccinating health workers in high-risk regions, a "ring" of likely exposed people, and close contacts of infected persons. They warned that these efforts should begin as quickly as possible.

"Curtailing an outbreak is always easier in its earliest stages than after it has disseminated geographically," the researchers wrote. "That window of opportunity may be rapidly closing."

Reflecting on the public health community's past efforts to make a vaccine for Ebola, Cox says the virus was not on anyone's radar. Nobody thought Ebola would be a public health crisis, she says, "but as we infringe on the animal kingdom we will continue to have these viruses."

In a way, Cox is torn about the Ebola vaccine. She and many of her colleagues say the work is a moral response to the situation in West Africa. "There is a thing called social responsibility," Cox says.

But she is self-funding the effort, and her duty to shareholders limits what she is willing to put toward the project. Asked what Protein Sciences has spent on the vaccine, she says, "It is a limited expenditure.

"It is possible with more resources, we could have done this quicker," Cox says. "We felt we had to step out on the boat, but there it stops."

For Cox, "there" is in clinical trials, an expensive step in the development of any drug, one she hopes an official public health body, like the NIH, or another pharmaceutical company could pursue.

"If you have a technology that could be used to deal with a public health crisis you have to make clear that show to make an effort but at the same time you have to be realistic," she says.

The vaccine Protein Sciences is developing is not a weakened version of the Ebola virus. In fact, Protein Sciences is able to develop the vaccine without ever putting its employees' hands on a live version of the virus.

Ebola virus is a filovirus, so named because of its filament- or threadlike shape. On the outside of the long virus are glycoproteins, little arms or branches that connect with cells. These proteins are what the immune system sees and, importantly, what it needs to recognize to launch an immune response.

Infections of Ebola accelerate and spread very quickly in the body, much faster than the time it takes the immune system to recognize the virus cells as foreign and dangerous. By the time the body catches up, the virus has spread far through the body, causing internal hemorrhaging and organ failure.

The vaccine introduces the immune system to what Ebola looks like, giving it weeks to learn that the glycoprotein is a foreign particle and requires a serious response.

Producing the glycoprotein involves some genetic hijacking. Protein Sciences starts with a virus that is native to worms called a baculovirus. Researchers reprogram the virus' genetic code by rewriting specific parts of its genes, giving the virus a new set of instructions — that is, to produce as many copies as it can of the glycoprotein that pockmarks the outside of Ebola.

Researchers then introduce the baculovirus to cells of the Fall armyworm, known as Spodoptera frugiperda, and the mixture produces a soup of material, a small amount of which is the treasured vaccine protein.

Research has shown that the proteins need a helper called an adjuvant to trigger the strong immune response needed with Ebola. The adjuvant acts as a structure for the proteins to hang on.

Cox is in talks to acquire an adjuvant for the company's vaccine. Having the adjuvant, Cox says, gives the company the best chance for its vaccine to get approval from the FDA.


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