First use of Ebola vaccine appears at least a month away

A vaccine that could help protect medical workers as they fight Ebola in West Africa, even just after contamination, may take at least a month to be available as global officials weigh its safety.

The sudden donation of as many as 1,000 doses of a vaccine that hasn't been tested in humans is creating a conundrum because they could go to healthy people, rather than those already infected. A World Health Organization ethics panel this week decided that people in West Africa should be allowed access to promising experimental treatments or vaccines.

"I would personally not hesitate to take that vaccine," said Thomas Geisbert, a virologist at the University of Texas Medical Branch and a developer of the vaccine donated to WHO by the Canadian government. "I've seen it used in many, many non- human primates. Never saw a problem with it."

The WHO will review data on the vaccine's design and results from animal studies to assess its safety, said Marie- Paule Kieny, the assistant director-general for health systems and innovation. It would then discuss which countries would get the doses, and in what quantities, she said.

All of that may take at least a month, Kieny said. "We cannot just take any vial of anything and start distributing it," she said in an e-mail.

While the WHO studies the product, Canada will keep the donated doses in Winnipeg, where the vaccine was developed, Shelly Glover, minister of Canadian heritage and official languages, said in a news conference with reporters.

"In the meantime, they remain here in Winnipeg ready to go at a moment's notice," Glover said.

1,000 Deaths

Health officials are weighing the risk of using unproven products as the disease has killed more than 1,000 people and teams of researchers rush to get their vaccines into clinical trials. The outbreak, the worst since the virus was first identified in 1976, has raged through Sierra Leone, Liberia and Guinea and recently reached Nigeria, Africa's most populous nation. Modupeh Cole, a prominent Sierra Leone doctor treating Ebola patients, died after being infected, the government reported yesterday.

Renewed focus on vaccines was sparked by the donation of 800 to 1,000 vials to the WHO by the Canadian government. The vaccine, called VSV-EBOV, was developed by Canada's National Microbiology Laboratory and is licensed by Ames, Iowa-based NewLink Genetics Corp.

While vaccines normally are preventative, VSV-EBOV has also shown effectiveness in animal studies after exposure to the virus. It could be used soon after someone has contact with an infected person, much like a rabies shot, said Gary Kobinger, chief of special pathogens for the Public Health Agency of Canada.

Five Candidates

Besides VSV-EBOV, there are four other vaccine candidates getting support from the U.S. National Institutes of Health. The most advanced experimental product is being developed in conjunction with GlaxoSmithKline Plc. The vaccines work by delivering benign Ebola genes into the body in such a way that they stimulate an immune response to protect against future infection.

Glaxo's candidate and VSV-EBOV are scheduled to begin clinical trials assessing safety in humans by the end of September.

Glaxo is "talking to regulators and the World Health Organization to see what we can do to accelerate the process," Catherine Hartley, a spokeswoman for the London-based drugmaker, said in a telephone interview. "Until we know it is safe, it is very hard to think about how and when and who it might be used for."

Human Trials

The trial with Glaxo's vaccine will enroll 20 healthy adults, Jennifer Routh, an NIH spokeswoman, said in an e-mail.

NewLink, a partner with Canada, is also working "around the clock" to start trials, president Nicholas Vahanian said in a telephone interview.

The company reserved enough of the vaccine for testing and made a joint decision with the Canadian government to donate the rest, according to Vahanian. NewLink's trial will have 39 people, said Brian Wiley, vice president of business management.

NewLink also is negotiating with manufacturers to ramp up production, aiming for 10,000 doses within months, Wiley said in a phone interview.

Safety First

Some researchers are calling for officials to slow down and wait for safety data.

"Premature deployment of unproven interventions could cause inadvertent harm, compromising an already strained relationship between health care professionals and patients in West Africa," Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, wrote in the New England Journal of Medicine today. "Should exemptions be offered for compassionate or emergency use, distribution of scarce interventions must be conducted with careful ethical guidance and regulatory review."

Safety trials are essential because "if something goes wrong with a vaccine, you have harmed a healthy individual," said John Eldridge, chief scientific officer for Profectus BioSciences Inc., based in Baltimore.

Animal Results

Profectus also has an experimental Ebola vaccine that can completely protect monkeys from the virus, which could enter clinical trials in a year, he said.

It would be risky to perform initial safety tests in Africa where patients may be far from a good hospital that can provide modern medical care should something go wrong, said Hildegund Ertl, a professor of immunology at The Wistar Institute in Philadelphia.

"You need a safety trial in a country where you have easy access to health care before you go into rural Africa," she said.

During an outbreak it would probably be difficult to conduct a controlled trial in which some people got a placebo and others a vaccine. The lack of such data means scientists are unlikely to get an unambiguous answer to the question of how well a vaccine works, she said.

Informed Audience

Health workers on the front lines would be the ideal audience for a vaccine, as they may be in a better position to grasp the danger of an unproven shot, said G. Kevin Donovan, director of the Pellegrino Center for Clinical Bioethics at Georgetown University.

"It's ethically a more tolerable situation in that health- care workers are presumably more medically sophisticated and understand the risks and benefits," he said in a telephone interview.

Since the vaccine doses being donated by Canada are being considered for compassionate use, it means they would "likely be limited to post-exposure," a spokeswoman for Doctors Without Borders said in an e-mail. "It would ideally have to be administered within 24 or 48 hours of a person being exposed to Ebola virus." The non-profit organization has 676 staff members working in Guinea, Sierra Leone and Liberia.

There is no cure for Ebola, which is spread by contact with blood and other bodily fluids. The virus has killed 1,069 of 1,975 people afflicted in the four West African nations as of Aug. 11, the WHO said yesterday.

The disease is normally treated by keeping patients hydrated, replacing lost blood and using antibiotics to fight opportunistic infections. The hope is that a patient's immune system will eventually fight off the virus's aggressive attack.

Nancy Kass, a professor of bioethics and public health at the John Hopkins Berman Institute of Bioethics in Baltimore, is among those urging a gradual roll out for the Canadian vaccine.

"If there was some crazy side effect in 24 hours, you'd hate to think that 50 people were vaccinated in one day," she said.