High effectiveness found in Guinea Ebola ring vaccination trial

A ring vaccination trial in Guinea of a Canadian-developed Ebola vaccine showed it was highly effective against the disease, setting the scene for it quickly to become a useful response tool.

Researchers found that the vaccine was 100% effective in people who received it soon after possible exposure. The vaccine, called VSV-EBOV, uses an Ebola protein spliced into a vesicular stomatitis virus (VSV). It was developed in Canada and is licensed by NewLink Genetics and Merck.

A World Health Organization (WHO)–sponsored team published the findings today in an early online edition of The Lancet.

An independent group that reviewed the findings urged that the trial continue, to look for more conclusive evidence on its ability to provide populations with "herd immunity" against the disease.

Margaret Chan, MD, MPH, WHO director-general, said in a statement, "This is an extremely promising development." Crediting Guinea's government, its communities, and research partners, she added, "An effective vaccine will be another very important tool for both current and future Ebola outbreaks."

Some had 100% protection

The ring vaccination trial of VSV-EBOV launched in Guinea in late March. The same strategy was used to eradicate smallpox in the 1970s, and the Ebola trial's goal is to see if a similar tactic can help tamp town Ebola hot spots before they morph into large outbreaks.

Researchers evaluated a single dose of the vaccine in rings of contacts of Ebola patients. About 4,000 close contacts of nearly 100 Ebola patients participated in the trial. Half of the rings were vaccinated immediately after an Ebola case was identified. As a control group, half of the rings were vaccinated 3 weeks after an infection was confirmed. The vaccine was also given to 1,200 of Guinea's frontline Ebola response workers.

At a media telebriefing in Geneva today, Marie-Paule Kieny, PhD, the WHO's assistant director-general for health systems and innovation, said none of the 2,014 people who were immediately vaccinated got sick with Ebola 10 days after they were vaccinated. However, 16 people in the 1,498-person delayed vaccine group contracted the disease. So far the analysis shows 100% protection, Kieny said, adding that the 95% confidence interval was 75% to 100%, with a P value of 0.0036.

The WHO's independent panel looked at the trial results on Jul 3 and recommended that randomization will be stopped, and all rings will be vaccinated immediately. Also, based on new safety data, adolescents ages 13 to 17 will now be included in the rings, and possibly 6- to 12-year-old children.

Wider use as an outbreak response tool could still be months away, because the vaccine needs to go through licensing, Kieny said. Another WHO group—the Strategic Advisory Group of Experts (SAGE)—will examine the findings and make a recommendation on how the vaccine should be used.

While VSV-EBOV appears to elicit robust immunity quickly, WHO vaccine experts are considering two types of vaccines to target different needs in outbreak settings, she said. One is a vaccine such as VSV-EBOV that triggers robust immunity quickly, to knock down hot spots, and another would be a product that confers long-lasting immunity, which would be useful for people such as healthcare workers and burial team members.

Optimism—with key questions

Michael T. Osterholm, PhD, MPH, director of the University of Minnesota's Center for Infectious Disease Research and Policy, which publishes CIDRAP News, called today's trial report "a remarkable piece of public health work." He was part of a group that in February published a report on criteria for fast-track development of Ebola vaccines.

The results have significant consequences not just for West Africa's outbreak, but also for future outbreaks, he said. Use of the vaccine in neighboring Liberia and Sierra Leone, however, as well as in other countries, faces licensing hurdles, which are, at best, complicated, he added.

There's still a critical need to understand how the other vaccine that is furthest along in clinical trials—ChAd3—performs, a product that could also play a key role in control efforts, Osterholm said. VSV-EBOV provides rapid protection, but researchers still have to resolve how long its protection lasts. ChAd3 uses a modified chimpanzee adenovirus vector. It was developed by GlaxoSmithKline (GSK) and the National Institute of Allergy and Infectious Diseases (NIAID).

In a statement from Doctors without Borders (MSF) today, its medical director Bertrand Draguez, MD, said more data are needed to spell out how effective the vaccine really is, and researchers need to clarify how soon protection sets in and lasts, but today's results represent a "unique breakthrough."

He said that adding a new prevention tool can help break up transmission chains more quickly, and governments in affected countries should start using the vaccine as soon as they can within the framework of the existing trial. Draguez, though, emphasized that it's crucial to keep the traditional pillars of Ebola response in place, including contact tracing, health promotion, and isolating sick patients.

'Remarkable' achievement

"A remarkable scientific and logistical achievement" is what The Lancet's editors called the findings today in a short commentary accompanying the report.

They observed that it took hard work and the help of family and friends in many small, scattered communities in Guinea to track down the immediate and secondary contacts of Ebola patients.

"That such a trial was even possible is a testament not only to the skill of the research teams but also to the commitment of communities to defeating an epidemic that has devastated their nation," the editors said. "Over 90% of the study's staff were from Guinea. Before this work, no clinical trial on this scale had ever been performed in the country."

The editors said more data on the vaccine's efficacy will be needed before it can be widely deployed. In the meantime, a group under WHO leadership has been laying the groundwork for its introduction.

Besides producing evidence of the vaccine's efficacy, the study demonstrates "the power of multilateralism and inclusive partnership to devise and execute critical clinical research," the editors wrote. "Out of this epidemic has come the opportunity to build unprecedented collaborations to generate evidence to advance health."

Praise from D. A. Henderson

The study and its results also drew praise today from Donald A. Henderson, MD, who led the WHO drive to eradicate smallpox in the 1960 and 1970s and who was part of the team that designed the trial. He holds the title of Distinguished Scholar at the University of Pittsburgh Medical Center's Center for Health Security, among other positions.

In an interview, Henderson observed that the researchers pushed on with the trial even though the epidemic appeared to be dying out. "The results are really quite remarkable," he said. "This is a live vaccine; it looks like it has the characteristics of smallpox [vaccine]: a single inoculation and an individual is protected."

Noting that no Ebola cases occurred in the immediate-vaccination group, Henderson said the vaccine's ultimate effectiveness won't be 100%, an impossible goal, "but it's going to be very high. I'd say that this is a marvelous work that the teams have done, because it's been very hard to work in these countries and do as they did in problem areas. They really went about it in a very solid and thoughtful way."

"You also have to be a little cautious," Henderson added. "You hope the next batches of vaccine will be the same. We think they would be, but we always have surprises. I'd say at this point I'm very optimistic, but I also have been bitten unexpectedly in instances where I thought we were in great shape. Cautious optimism is really the answer."

The ring vaccination strategy used in the trial was "pretty much" the same as was used to eradicate smallpox, he said. The general approach in the smallpox effort was to vaccinate the patient's family and any visitors, and perhaps vaccinate the 10 or 15 neighboring households if enough vaccine was available.

The Guinea study approach was to vaccinate the direct contacts of the patient and also the secondary contacts, or "contacts of the contacts." Henderson remarked that it's not always simple to distinguish between the primary and secondary contacts. "This can get pretty diffuse," he said, and if the lines are drawn too broadly, the effort can turn into a mass vaccination campaign, he observed.

Henderson said the vaccine looks effective enough to warrant deploying it quickly in the case of an Ebola resurgence or a new outbreak.

"If there were another one, I'd move it in quickly and do a focused ring vaccination," he said "It's certainly warranted to go ahead."

See also:

Jul 31 Lancet study

Jul 31 Lancet editorial

Jul 31 WHO press release

Jul 31 WHO vaccine telebriefing audio file

Jul 31 MSF statement

Mar 25 CIDRAP News story "Ebola vaccine trial launches in Guinea; Chinese vaccine test detailed"

Feb 17 CIDRAP/Wellcome Trust report: "Recommendations for Accelerating the Development of Ebola Vaccines"

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