London School of Hygiene & Tropical Medicine

A global consortium is supporting the Government of the Democratic Republic of the Congo (DRC) to introduce a second investigational Ebola vaccine as part of ongoing efforts to contain the outbreak in eastern DRC.

The large-scale clinical trial, sponsored by the London School of Hygiene & Tropical Medicine (LSHTM), is designed to help prevent the spread of the epidemic, the second worst in history, beyond the currently affected areas in eastern DRC, and if possible gather crucial information about the effectiveness of the vaccine to be better prepared to fight Ebola in the future.

The consortium is led by the DRC Ministry of Health (MOH) and Institut National de Recherche Biomédicale (INRB) and includes LSHTM, the Coalition for Epidemic Preparedness Innovations (CEPI); Médecins Sans Frontières (MSF) and Epicentre; with the Wellcome Trust contributing critical strategic guidance. Janssen Vaccines & Prevention B.V. is donating the experimental vaccine regimen for the study undertaken by the consortium.

The two-dose Ebola vaccine regimen (Ad26.ZEBOV, MVA-BN-Filo) is manufactured by the Janssen Pharmaceutical Companies of Johnson & Johnson. It was developed in collaboration with global partners, including Bavarian Nordic A/S, the U.S. Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services (HHS), the Innovative Medicines Initiative (IMI) funded through the European Union Horizon 2020 Programme, and the U.S. National Institutes of Health (NIH) at HHS.

The introduction of this second vaccine was recommended by the World Health Organization’s Strategic Advisory Group of Experts on Immunization in May 2019 to complement ongoing use of another investigational vaccine, rVSV-ZEBOV, made by Merck Pharmaceuticals. The Merck vaccine is being used in a ring vaccination strategy targeting contacts of those with Ebola virus disease and other health and frontline workers at high risk.

More than 6,500 people have taken part in multiple previous and ongoing clinical trials of the Janssen Ebola vaccine regimen. The available data indicate that the vaccine is well tolerated and induces robust immune responses to the Zaire strain of Ebola virus – the cause of the DRC outbreak. At present, there are no human data on efficacy in preventing Ebola virus infection.

In 2019 researchers in Uganda began a two-year clinical trial of the vaccine among healthcare and frontline workers. The vaccine is also undergoing evaluation along with the Merck vaccine as part of a large Phase 2 randomized, placebo-controlled trial in West Africa called PREVAC that began in 2017.

Ad26.ZEBOV, MVA-BN-Filo will be offered to adults and children aged one year or older under a clinical trial protocol that aims to evaluate the effectiveness and safety of the vaccine in an outbreak setting. The regimen includes two doses (one of Ad26.ZEBOV and the second of MVA-BN-Filo), spaced two months apart.

Janssen will donate up to 500,000 doses of the vaccine regimen for those in communities near the outbreak who are considered at risk, as determined by the DRC MOH, INRB and consortium partners, taking into account the latest epidemiological data on disease spread, as well as logistical and security concerns.

Dr Eteni Longondo, Minister of Public Health, DRC, said: “As part of our Ebola response efforts, the Government of DRC plans to introduce a second experimental Ebola vaccine within a clinical trial protocol. It’s vital that we intensify our efforts. That’s why we’re working with international partners to provide our response teams with another tool to fight and ultimately stop the spread of this terrible disease.”

The study will be implemented by the INRB and MOH, supported by MSF, Epicentre, and LSHTM under the leadership of the Principal Investigator Dr Jean-Jacques Muyembe, INRB Director General and head of the DRC multisector Ebola response committee.

Dr Muyembe said: “The current Ebola outbreak is concentrated in North Kivu and Ituri provinces, areas which have had to deal with insecurity and violent conflict. This environment has complicated response efforts and led to distrust of health care workers, which has become a major problem. Therefore, effective community engagement will be absolutely critical to the successful introduction of a second Ebola vaccine. Deploying any vaccine in these circumstances is enormously challenging and must be done alongside a range of other public health measures and interventions, such as contact tracing. But building trust and confidence within affected communities must be our priority.”

The trial will be sponsored by LSHTM.

Professor Daniel Bausch, Co-Principal Investigator of the trial and Director of the UK Public Health Rapid Support Team, a partnership between LSHTM and Public Health England and funded by UK aid from the UK Department of Health and Social Care, said: “We are pleased to play a major part in this important trial and look forward to working closely with the Government of the DRC, partners and local communities. The death toll from this outbreak has now reached more than 2,000, and cases of Ebola continue to be identified. Clearly, we need to use every tool at our disposal to bring this outbreak to an end.

“Deployment under study conditions of a second experimental vaccine will have the dual benefit of supporting the ongoing response and improving preparedness for future outbreaks. The two vaccines will be used in complementary fashion. The Merck vaccine will continue to be given in a ring vaccination approach to contacts of persons with Ebola and frontline workers, while the Janssen vaccine will be used to protect individuals in surrounding areas from contracting the Ebola virus.”

Paul Stoffels, M.D., Vice Chairman of the Executive Committee and Chief Scientific Officer of Johnson & Johnson, said: “No single entity can solve this outbreak which has continued for more than a year. The global health community has come together in support of this initiative using Janssen’s investigational Ebola vaccine regimen to help prevent its further spread. This collaboration is essential, and a great demonstration of how the public and private sectors can work together to help tackle a public health crisis.”

Professor Peter Piot, Director of the LSHTM, said: “The continuing severity of the Ebola outbreak in DRC requires a concerted effort using all interventions available. I am delighted by the DRC authorities’ decision to introduce the Janssen Ebola vaccine as a second investigational vaccine, providing their teams on the ground with another vital tool to fight this deadly outbreak. The DRC is a leader in innovation during Ebola outbreaks, and remains at the forefront of research and innovation in this area. LSHTM is proud to be working alongside the DRC Government, INRB and the wider consortium partners to tackle this outbreak which is now in its 15^th month. The large-scale study should also strengthen global preparedness for future Ebola outbreaks.”

John Johnson, Project Lead for Ebola Vaccination for MSF, said: “MSF is adding to the operations we already have in DRC by participating in this study. We see the study as an additional opportunity to offer our field experience and expertise working with communities and partners on the ground to fight against Ebola.”

As the Ad26.ZEBOV, MVA-BN-Filo vaccine is not licensed for use, people will be offered the vaccine regimen under a carefully monitored clinical trial protocol, which has been approved by the DRC MOH National Ethics Committee, the Ethics Committee of the School of Public Health at the University of Kinshasa and the DRC national regulatory authority, Direction de la Pharmacie et du Médicaments.

The trial will be funded by CEPI, the European Union, UK Department for International Development, Wellcome and the Paul G. Allen Family Foundation.