London School of Hygiene & Tropical Medicine

Tests of the experimental Ebola vaccine VSV-ZEBOV in over 7,500 participants in Guinea suggest that the vaccine provides high protection against the disease as early as ten days after vaccination, in adults who have potentially been exposed to the virus by coming in close contact with a recently infected person.

The research, published in The Lancet, suggests that the vaccine is safe, and also provides the first evidence that unvaccinated people may be indirectly protected from Ebola virus disease (EVD) when the VSV-ZEBOV vaccine is delivered using a ring vaccination strategy.

Ring vaccination, which was used in the past to eradicate smallpox, is intended to create a buffer of protection to prevent the spread of the disease, by vaccinating and monitoring the contacts, and contacts of contacts (the "ring"), of each newly diagnosed Ebola case.

The Ebola ça Suffit trial, led by the World Health Organization (WHO) with Ministry of Health of Guinea, Médecins sans Frontières (MSF), EPICENTRE, the Norwegian Institute of Public Health, the London School of Hygiene & Tropical Medicine and other partners, in Basse-Guinea, where Ebola has persisted.

Whenever a person was diagnosed with Ebola, the researchers traced all individuals who may have been in close contact with this 'index' case. Adult contacts aged 18 or older who were not pregnant or breastfeeding were offered the vaccine. If consent was given, adults in the ring were randomised to receive either immediate or delayed (by 21 days) vaccination. The delayed vaccination group acts as a control group, and allows all consenting contacts to be vaccinated during the trial, and then visited at home repeatedly to record any adverse events.

In the 90 clusters who received either immediate or delayed vaccination, a single injection of VSV-ZEBOV gave complete 100% protection against EVD 10 days after randomisation. No cases of EVD were recorded 10 days after randomisation in the immediate group, compared to 16 cases in the delayed vaccination clusters.

Dr Marie-Paule Kieny, Assistant Director-General of the which sponsored and led the study, said: "Before the trial started, in most clusters there had been a series of Ebola cases over the weeks prior to randomisation. However, since the trial started, we have seen no new cases in vaccinated volunteers within 10 days of vaccination, regardless of whether vaccination was immediate or delayed."

Study co-author John Edmunds, Professor of Infectious Disease Modelling at the London School of Hygiene & Tropical Medicine, whose team helped design the trial, said: "This is very encouraging news. This trial indicates not only that the vaccine appears to prevent Ebola, but also that the policy of ring vaccination is likely to be very effective at helping to stamp out the remaining cases."

Peter Smith, Professor of Tropical Epidemiology at the London School of Hygiene & Tropical Medicine, was one of the advisors on the design of the trial and chairs the funding committee for Global Health and Vaccination Research (GLOBVAC) of the Research Council of Norway, which provided initial funding for the trial.

Prof Smith said: "The interim results of the trial, using a novel evaluation approach, are very exciting and suggest that the Ebola vaccine tested may be highly effective in protecting against Ebola disease among those in the immediate vicinity of an Ebola case. If these results are confirmed as the trial continues, the ring vaccination strategy may be important not only in contributing to ending the current epidemic, but will also be deployable to contain rapidly any future outbreaks of Ebola disease."

VSV-ZEBOV was developed by the Public Health Agency of Canada and is licensed to NewLink Genetics and Merck. The vaccine works by replacing a gene from a harmless virus known as vesicular stomatitis virus (VSV) with a gene encoding an Ebola virus surface protein. The vaccine does not contain any live Ebola virus. Earlier trials have shown VSV-ZEBOV to be safe and to produce consistently powerful immune responses in adults, thought to be important for protection against Ebola.

The sponsor of the study is the World Health Organization (WHO); it is implemented by the Ministry of Health of Guinea, Médecins sans Frontières (MSF), EPICENTRE, the Norwegian Institute of Public Health and WHO. The trial is funded by WHO, with support from the Wellcome Trust (United Kingdom); MSF; the Norwegian Ministry of Foreign Affairs through the Research Council of Norway; and the Canadian government through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre and Department of Foreign Affairs, Trade and Development. The trial team includes researchers from the University of Bern, the University of Florida, the London School of Hygiene & Tropical Medicine, Public Health England, and the European Mobile Laboratory among others.

Secondary analysis for the trial suggests that ring vaccination also reduced the risk of contracting EVD for non-vaccinated individuals in the clusters. The trial is now continuing in order to generate more data for the assessment of vaccine efficacy and safety.

Publication

• Ana Maria Henao-Restrepo, Ira M Longini, Matthias Egger, Natalie E Dean, W John Edmunds, Anton Camacho, Miles W Carroll, Moussa Doumbia, Bertrand Draguez, Sophie Duraffour, Godwin Enwere, Rebecca Grais, Stephan Gunther, Stefanie Hossmann, Mandy Kader Kondé, Souleymane Kone, Eewa Kuisma, Myron Levine, Sema Mandal, Gunnstein Norheim, Ximena Riveros, Aboubacar Soumah, Sven Trelle, Andrea S Vicari, Conall H Watson, Sakoba Kéïta, Marie-Paule Kieny*, John-Arne Røttingen*. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. The Lancet. http://dx.doi.org/10.1016/S0140-6736(15)61117-5

Related links

• Full Lancet article (pdf) 
• Lancet Editorial comment (pdf)
• World on the verge of effective Ebola vaccine - WHO news release