Human trials for an Ebola vaccine have begun

There is concern that the Ebola virus disease (EVD) outbreak in West Africa is spiraling out of control (Reuters):

"The number of new Ebola cases in West Africa is growing faster than authorities can manage them, the World Health Organisation (WHO) said on Friday, renewing a call for health workers from around the world to go to the region to help. As the death toll rose to more than 2,400 people out of 4,784 cases, WHO director general Margaret Chan told a news conference in Geneva the vast nature of the outbreak -- particularly in the three hardest-hit countries of Guinea, Liberia and Sierra Leone -- required a massive emergency response."

Projections from mathematical modeling paint an increasingly dire picture with one possible outcome, if public health measures do not improve significantly, being the deaths of not thousands, but hundreds of thousands of people (NYTimes):

"The deadly Ebola outbreak sweeping across three countries in West Africa is likely to last 12 to 18 months more, much longer than anticipated, and could infect hundreds of thousands of people before it is brought under control, say scientists mapping its spread for the federal government."

However, it is important to note that "[t]he scientists who produced the models cautioned that their dire predictions were based on the virus’s current uncontrolled spread and said the picture could improve if public health efforts started to work."

The key unknown is the size and urgency of the World response to this catastrophe in terms of providing medical assistance. One big problem is that the medical infrastructure in the affected areas has been inadequate with understaffed and poorly equipped clinics overwhelmed by the number of patients so that many are left to die at the gates (Figure 1).

But it appears that the World is finally ready to act. On Tuesday President Obama announced that the U.S. will commit up to $500 million and 3000 military personnel to the battle. Additional field hospitals will be built with 1700 additional beds, and a training facility that can train up to 500 healthcare workers per week. This is a gigantic amount of aid and President Obama and the U.S. deserve to be commended.

There is more good news on a different front. Progress is being made developing anti-EV treatments. In previous posts, I described the drug ZMapp, which consists of three humanized monoclonal antibodies against Ebola virus proteins. ZMapp was given to two American patients who were brought back to the U.S. from Liberia, and it may have contributed to their eventual recovery. Along with this anecdotal evidence in humans, recent preclinical data show convincingly that ZMapp is effective curing monkeys of EVD even when administered several days after infection.

Another important treatment is a vaccine against EVD. This week the BBC reported that human trials of an Ebola virus vaccine have begun in England with 60 healthy volunteers being injected to test for safety. It was developed by the Swiss-Italian biotechnology company Okairos, which was bought by the pharmaceutical company GlaxoSmithKline. The vaccine is based on a chimp adenovirus vector that expresses a key Ebola virus protein (EV glycoprotein) on its surface. When injected into a person, an immune response is generated against both the adenovirus and Ebola virus glycoprotein, thus protecting against further infection by either.

In collaboration with scientists at the NIH, trials have been performed in monkeys, which are a good model system for human vaccination. In recently published work, researchers showed that all macaques monkeys that received the vaccine were able to survive Ebola virus infection with no detectable virus in the blood, whereas all of the unvaccinated control macaques died to the infection by day 6. This is a promising preclinical result.

In addition, another pharmaceutical company Johnson & Johnson (J&J) will start in early 2015 human clinical trials of its vaccine, which is a combination two vaccine candidates, one from J&J and the other from a Denmark-based biotech company Bavarian Nordic (WSJ). As reported by the company, early preclinical data indicate that the combination is effective.

Thus, despite the frightening projections, steps are being taken to contain the Ebola virus outbreak. Furthermore, in the longer term, promising drugs are being developed and tested so that this epidemic may be the last major outbreak of Ebola virus disease.

Figure 1. Ebola patient left to die outside of Liberian hospital (NYTimes).