Ebola vaccine turned down by WHO now best hope amid outbreak

The calls started coming in August to the office of GlaxoSmithKline Plc Chief Executive Officer Andrew Witty from the head of the World Health Organization, Margaret Chan. The Ebola outbreak was raging out of control and Chan needed the drugmaker's vaccine as quickly as possible.

The sudden sense of urgency for an Ebola vaccine was an about face from a few months earlier when Glaxo contacted the WHO, asking whether its vaccine could help with the outbreak. At that time, the company was told the focus was on containment and the WHO didn't have a policy for using vaccines in this type of situation. "We'll get back to you" was the message, said Ripley Ballou, head of Glaxo's Ebola vaccine program.

As those months passed and containment efforts failed, the epidemic spun out of control, claiming more lives than all past outbreaks combined. So far, more than 6,200 people have been infected and 2,900 have died, and the virus could sicken more than 1.4 million people by January under the worst-case scenario projected by the U.S. Centers for Disease Control and Prevention.

With no approved Ebola medicines, and experimental treatments in short supply, a vaccine is now one of the best hopes for halting the virus's spread before it becomes entrenched in the region. That puts pressure on the few drugmakers with a vaccine in development as they shift resources, delay other projects, and spend millions in a race to immunize patients. Glaxo and Johnson & Johnson are preparing thousands of doses of their experimental vaccines to test in Africa as early as January.

"It may be that without a vaccine we can't really stop this epidemic," Peter Piot, a co-discoverer of the Ebola virus in 1976 who is now the director of the London School of Hygiene and Tropical Medicine, said at a news conference in London this week.

When Glaxo contacted the WHO in March, the vaccine was seen as a "diversion of energy" at a time when it was believed the outbreak would be controlled with traditional measures, such as contact tracing and safe burials, that have helped contain every previous outbreak, said Marie-Paule Kieny, the WHO's assistant director-general for health systems and innovation. At the end of March, there were about 100 cases of Ebola in Guinea, with early reports the virus was spreading to Liberia and Sierra Leone, according to the U.S. Centers for Disease Control and Prevention.

"We were in a situation where GSK had a vaccine which had been tested in animals, and that was it," Kieny said in a telephone interview. "It was only then when the situation started to be quite worse, and people understood that we're not going to make it, that the effort came to a higher level."

After receiving the request from Kieny and Chan last month, Glaxo pulled 20 people off various projects, many from its malaria vaccine program, one of its most highly publicized research initiatives, and assigned them full-time to the Ebola vaccine.

The company is aiming to have 10,000 to 15,000 doses by January to start vaccinating health-care workers on the front lines of the Ebola outbreak as part of the next stage of testing. Glaxo will need six months to figure out how to eventually produce hundreds of thousands of doses for wider use, Ballou said.

The U.K. government, the non-profit Wellcome Trust, and the Medical Research Council, a U.K. research-funding organization are finding the production of about 10,000 doses. Gavi, the world's biggest funder of vaccines for developing countries, which is backed by the Bill & Melinda Gates Foundation, said today it is examining how it can help accelerate the availability of Ebola vaccines.

Glaxo is among at least five companies that have announced plans to start human testing of an Ebola vaccine, including Johnson & Johnson, Inovio Pharmaceuticals Inc., NewLink Genetics Corp., and Profectus Biosciences Inc.

Glaxo started giving doses to healthy volunteers in the U.K. and U.S. this month. Within the next four weeks, as many as six different trials will be under way in the U.S., U.K., Switzerland and Mali. Early results on the safety and efficacy of the Glaxo and NewLink shots, the most advanced in development, should be available by November, Kieny said. The agency plans to meet with the two companies next week to discuss the simultaneous roll out and testing of the vaccines in Africa, which may happen in January, Kieny said.

"This is unprecedented, because you are talking about quite a big financial investment into something which has not proven anything for the time being," she said.

Until a few months ago, Glaxo's vaccine got little attention out of the London-based company's hundreds of experimental compounds, and the drugmaker has been "essentially starting from ground zero," said Ballou. Glaxo acquired the vaccine last year as part of its $324 million purchase of Okairos AG, which has inoculations in more advanced stages of testing for hepatitis C and malaria.

"It wasn't really until the first week in August when it was clear that the epidemic was something very different from what we had ever seen before that WHO came to us and said we really need you to accelerate this vaccine," Ballou said. "Within 24 hours, we had all of our partners on the phone."

Three weeks later, the first patient received the vaccine to kick off the early-stage human trials. "That's an amazingly fast process," he said.

Glaxo's vaccine is a chimpanzee cold virus that is injected with a small piece of the Ebola virus gene, which tricks the body into making an immune response against Ebola, even though it hasn't been infected with the disease. The virus is grown in an Okairos facility in Rome in plastic so-called wave bags, which rock back and forth on a platform.

Not far behind Glaxo in the race to get a vaccine to patients is Johnson & Johnson, which plans to start human testing in March. J&J expects to have hundreds of thousands of doses available through the course of 2015 and more than a million in 2016, said Paul Stoffels, the New Brunswick, New Jersey-based company's chief scientific officer.

Stoffels began ramping up work on the vaccine on his own, without prodding from the WHO, as he saw Ebola beginning to accelerate and making its way into cities in West Africa.

He knew first-hand the devastation it could cause. In 1995, a few years after completing his training as an infectious disease doctor at a hospital in Kikwit, in what is now the Democratic Republic of Congo, Stoffels got a call from the nuns he'd worked alongside there. They were in desperate need of antibiotics for what they believed was bloody diarrhea. He would soon learn it was much worse: his former colleagues were infected with Ebola and would be among more than 250 who died in that outbreak.

"No one could have ever foreseen that this could happen," said Stoffels. "Now history is history and we have to start solving the problem."

J&J's vaccine has been more than a decade in the making. It started in 2002, in the labs of Netherlands-based Crucell, which J&J bought in 2010. Researchers at Crucell began work on an Ebola vaccine, though after four years halted work when a first study in humans found it wasn't potent enough to trigger the immune system to develop the necessary antibodies.

So the company went back to the drawing board in 2006 and came up with the current version. It uses a disarmed version of a cold virus to get Ebola's genetic information into cells. It's then combined with a second booster shot from biotechnology company Bavarian Nordic A/S of Denmark.

"We will have a good chance it will work, but there is no guarantee," said Stoffels. "We know we have to do our work step by step to get to the solution."

Testing a vaccine during an outbreak in a low-income country will come with big ethical and logistical questions. Researchers need to decide if the vaccine can be safely stored and transported, who should get it first and how to overcome patients' potential fear of foreign health interventions, said G. Kevin Donovan, director of the Pellegrino Center for Clinical Bioethics at Georgetown University.

Donovan said that starting with health-care workers would be the most ethical way to ensure those getting the vaccine are aware of the risks and can be properly monitored to assess the the vaccine's safety and efficacy.

"We are dealing with a whole new ball game given the magnitude of the current outbreak," said Donovan.

While Ebola was discovered in the 1970s, few researchers were pursuing a vaccine until after the Sept. 11, 2001, attacks when the U.S. began funneling millions to protect against bioterrorism.

The U.S. government passed an act in 2004 to set aside $5.6 billion over 10 years for the stockpiling of drugs and vaccines that could protect against a bioterrorism attack, creating a potential buyer for any company able to prove it had a safe and effective vaccine. It has also set aside millions in research grants from the National Institutes of Health.

Thomas Geisbert, a professor of microbiology and immunology at the University of Texas, was one of the early pioneers of Ebola vaccine research and has been hunting for a vaccine since the 1990s. At that time, he said, there were few labs with the capabilities to do testing on a pathogen as deadly as Ebola and not enough money to do the necessary experiments.

"All of a sudden there is all this money," said Geisbert, who has worked on the technology behind the vaccines being developed by NewLink and Profectus. "When you have more money, you can take more risks."

In recent years, the biggest barrier has been getting past the government bureaucracy to begin human testing -- something the urgency around the latest outbreak has helped cut down, Geisbert said.

The next steps won't be cheap or easy, said Stoffels. J&J must develop manufacturing capabilities for the vaccine, which must be made in a carefully controlled environment, and develop and implement a plan for testing it in volunteers.

"We will have to mobilize significant resources for this and we are doing that as we speak," said Stoffels. "It is a significant amount of work but the senior leadership is committed to doing it."

(A previous version of this story stated that Glaxo could have hundreds of thousands of doses in six months.)