Positive Phase 1 Data Announced for Ebola Vaccine Regimen

A public-private partnership of some of the world’s leading health organizations today announced that data from a Phase 1 study of a preventive Ebola vaccine regimen have been published in JAMA: The Journal of the American Medical Association. The results, the first published on the vaccine regimen, suggest that the regimen was well-tolerated by healthy volunteers and immunogenic (produced an immune response). Among the findings, 100 percent of participants in the study achieved an initial antibody response to Ebola, and this response was sustained 8 months following immunization. The study was led by the Oxford Vaccine Group at the University of Oxford Department of Paediatrics and took place in the United Kingdom.

The Ebola vaccine regimen is being developed by the Janssen Pharmaceutical Companies of Johnson & Johnson, in collaboration with Bavarian Nordic. The regimen was first discovered in a collaborative research program with the U.S. National Institutes of Health (NIH). Clinical studies have been supported by grants awarded by Europe’s Innovative Medicines Initiative (IMI) to a consortium of leading global research institutions working with Janssen, which includes the London School of Hygiene & Tropical Medicine, the University of Oxford and Inserm, the French National Institute of Health and Medical Research.

“The Ebola crisis in West Africa left a huge human cost, we continue to see flare-ups of this disease, and the world needs to be far better prepared for the next major outbreak,” said Paul Stoffels, M.D., Chief Scientific Officer, Johnson & Johnson. “This study suggests that Janssen’s investigational prime-boost vaccine regimen, if approved by regulators, could be an important tool in global strategies to help prevent another Ebola epidemic.”

The Phase 1 study tested a vaccine regimen containing two components based on, respectively, AdVac technology from Crucell Holland B.V., one of the Janssen Pharmaceutical Companies, and MVA-BN® technology from Bavarian Nordic A/S. Healthy volunteers were given one vaccine dose to prime their immune system, and then the alternative vaccine to boost their immune response, with the goal of evaluating the duration of immunity. Prime-boost vaccination is an established approach for the prevention of several infectious diseases.

“Recent evidence highlighting the persistence of the Ebola virus in bodily fluids, and the potential for sexual transmission from Ebola survivors, reinforce the importance of finding a robust and durable vaccine for this disease,” said Dr. Matthew Snape of the Oxford Vaccine Group and the study’s lead author. “These results show that an initial immune response with AdVac immunization is enhanced by MVA-BN boosting, generating sustained immunity that has the potential to provide durable protection from Ebola in at-risk populations.”

In the study, most participants were randomized in a blinded fashion to receive either vaccine or placebo, while some individuals were in an open-label group receiving vaccine. Among the randomized participants, 97 percent generated antibodies specific to Ebola four weeks after a priming dose with AdVac. Additionally, more than half of AdVac recipients developed Ebola-specific T cells, a key marker of cellular immunity. Validating the prime-boost concept, these immune responses were enhanced by administration of the MVA-BN booster dose, with 100 percent of participants generating Ebola-specific antibodies at 21 days post-boost, and
79-100 percent showing T cell responses depending on the dosing interval.

Notably, 8 months following prime vaccination, 100 percent of individuals in the study maintained Ebola-specific antibodies, while vaccine-induced T cell responses persisted in 77-80 percent of those receiving the AdVac/MVA-BN regimen.

In terms of safety, injection site pain was the most common reported adverse event, and was transient and generally of mild-to-moderate severity. Among randomized participants, fever was reported in 5 percent of AdVac recipients compared to 4.2 percent of those receiving placebo. In the open-label group, 27 percent of participants reported fever. All episodes of fever resolved within 24 to 48 hours. No serious vaccine-related adverse events were observed.

“Forty years after the discovery of Ebola, the world still needs an approved vaccine for this disease,” said Dr. Peter Piot, Director, London School of Hygiene & Tropical Medicine. “A durable prime-boost vaccine could be a vital asset in efforts to proactively protect the general population in countries that are vulnerable to Ebola outbreaks. And in light of the persistent challenges that we are seeing with the Ebola virus, durability has become a particularly important goal for vulnerable populations such as health workers and the families of Ebola survivors.”

“First of all, this study provides important validation for the concept of a prime-boost vaccination strategy against this disease,” said Yves Levy, CEO, Inserm. “Additionally, these data indicate that the vaccine regimen can induce two types of immune response – antibody-based and cellular – which together may have the potential to confer long-term protection against Ebola. These results are highly significant findings in the fight against Ebola in which Inserm has been involved since the very beginning.”

“We are delighted to see such positive results produced by a consortium supported with grants from the Ebola+ programme,” said Ruxandra Draghia-Akli, Director, Health Directorate, European Commission, and member of the IMI Governing Board. “These and the many other Ebola studies underway with the European Commission and IMI support show that cooperation research and public-private partnerships can be formed with great speed to develop innovative solutions for today’s most pressing global health threats. Only by joining forces as an international community can we prevent, control, and end pandemics.”

The Oxford study provides the first set of data from a total of 10 clinical studies that are being conducted on a parallel track across the U.S., Europe and Africa in support of potential eventual registration for the Ebola vaccine regimen. The first study of the vaccine regimen in a West African country affected by the recent Ebola outbreak began in Sierra Leone in October 2015.

Source: Johnson & Johnson