Ebola vaccine efficacy trial suggest vaccine provides high protection against disease

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.  The study was sponsored and led by the World Health Organisation (WHO).

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 (translation: “Ebola this is Enough”) trial took place in Basse-Guinea, the only area in Guinea with new Ebola cases at the start of the study on April 1, 2015. When a new (index) Ebola case was diagnosed, the researchers traced all individuals who may have been in close contact with this first case [2].  Adult contacts aged 18 or older (not pregnant or breastfeeding) were offered the vaccine. If consent was given, adults in the ring were randomised to receive either immediate or delayed (21 days after randomisation [3]) vaccination. Vaccinated volunteers were then visited at home on days 3, 14, 21, 42, 63, and 84 after vaccination to record any adverse events.

The study reports the incidence of EVD in the immediate rings compared to the delayed rings up to 20 July, 2015. In the 90 clusters who received either immediate vaccination (48; 4123 adults vaccinated) or delayed vaccination (42; 3528 adults vaccinated on day 21), a single intramuscular injection of VSV-ZEBOV gave complete (100%) protection against EVD 10 days after randomisation [4]. No cases of EVD were recorded 10 days after randomisation in the immediate group, compared to 16 cases in the delayed vaccination clusters (table 2).

“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,” explains co-author Dr Marie Paule Kieny, from the World Health Organisation (WHO) in Geneva, Switzerland.

Secondary analysis for the trial suggests that ring vaccination also reduced the risk of contracting EVD for non-vaccinated individuals in the clusters. The overall effectiveness of the vaccine in adults, including both those who consented to vaccination and those who did not, was 75% against EVD.  Additionally, in all members of the clusters, including non-vaccinated children and pregnant women, the risk of testing positive for EVD was reduced by around 76% (table 2 and figure 3).

The vaccine was well-tolerated – one vaccinated patient experienced an episode of fever, classed as a serious adverse event, that was found to be related to the vaccine.  Assessment of serious adverse events is ongoing as the trial progresses.

According to study co-author Professor John-Arne Røttingen, from the University of Oslo, Norway, “Our results are encouraging in that they suggest that ring vaccination could substantially reduce rates of Ebola virus disease in the community. Because the way that Ebola virus transmits has been shown to be consistent across countries and regions, we believe that these results are likely to be applicable to other regions of Guinea and to Sierra Leone and Liberia.  But whether this candidate vaccine could become a licensed vaccine for widespread use against Ebola outbreaks is still uncertain, and further evidence is needed to evaluate the safety and efficacy of the vaccine before it is used outside of a clinical trial setting.”

The study is an interim analysis of results from the Ebola ça Suffit trial, and the trial is now continuing in order to generate more data for the assessment of vaccine efficacy and safety.

A Lancet Editorial accompanying the Article states that, “This study will be the subject of intense scientific scrutiny and debate. But what do the results mean for those most at risk of Ebola virus infection in west Africa? The vaccine is not yet licensed. More data on efficacy are needed before it can be widely deployed. But if the evidence proves sufficient for licensing, a Global Ebola Vaccine Implementation Team, also under WHO's leadership, has been preparing the ground for its introduction-creating guidelines for the vaccine's use, strategies for community engagement, and mechanisms to expand country capacity for the vaccine's distribution and delivery. In addition, the GAVI Alliance has approved substantial funding for the procurement and deployment of the vaccine.”

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 and Tropical Medicine, Public Health England, and the European Mobile Laboratory among others.

FOOTNOTES:

[1] 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.

[2] This included contacts and contacts of contacts of the index case, around 50-100 people. Contacts included individuals who, within the last 21 days, lived in the same household, were visited by the index case after the onset of symptoms, or were in close physical contact with the patients’ body or body fluids, linen or clothes.

[3] This method is an alternative to using a placebo, but allows all consenting contacts to be vaccinated during the trial. The delayed vaccination group acts as a control group.

[4] Analyses of vaccine efficacy were restricted to events occurring 10 days or more after randomisation to account for the incubation period of Ebola and the unknown time for the vaccine to develop protective immunity.