Ebola virus disease (EVD) is a severe illness in humans, with case fatality rate between 25% to 90%, with an average of about 50%. The virus is transmitted to human from wild animals and spreads through human-to-human transmission.
The first EVD outbreaks occurred in remote villages in Central Africa, near tropical rainforests. The 2014–2016 outbreak in West Africa was the largest and most complex Ebola outbreak since the virus was first discovered in 1976, involving major urban and rural areas. More than 28,000 cases and more than 11,000 deaths were recorded.
The second largest Ebola outbreak occurred in mid-2018, in a conflict-affected region of the Democratic Republic of the Congo (DRC). As of July 2020, more than 3400 cases were reported, with about 2300 deaths since the outbreak was declared on 1 August 2018.
A range of potential treatments including blood products, immune therapies and drug therapies are currently under evaluation. Two monoclonal antibodies (Inmazeb and Ebanga) were approved for the treatment of Zaire ebolavirus (Ebolavirus) infection in adults and children by the US Food and Drug Administration in late 2020. The largest-ever Ebola vaccine campaign was a key factor in containing its spread. The introduction of two experimental vaccines involved inoculation of more than 350,000 people.
Twelve candidate Ebola vaccines (including monovalent, bivalent and multivalent candidates) have undergone or are currently undergoing clinical development at different trial phases, and two have obtained approval.
- rVSVΔG-ZEBOV-GP (Ervebo)
An rVSV-vectored candidate vaccine (rVSVΔG-ZEBOV-GP), consists of a vesicular stomatitis virus (VSV), which is an animal virus that causes flu-like illness in humans. The VSV has been genetically engineered to contain a protein from the Zaire Ebola virus so that it can induce an immune response to the Ebola virus.
The vaccine was studied in a Phase 3 trial involving 11,841 people during 2015. Among the 5,837 people who received the vaccine, no Ebola cases were recorded 10 days or more after vaccination. In comparison, there were 23 cases recorded 10 days or more after vaccination, among those who did not receive the vaccine. The trial was led by WHO, together with Guinea’s Ministry of Health, Médecins sans Frontieres and other international collaborators. This is the only study that has reported clinical efficacy and effectiveness for a candidate Ebola vaccine, which was shown to be safe and protective against the Zaire strain of the Ebola virus. A single dose of rVSVΔG-ZEBOV-GP has shown 100% efficacy (95% confidence interval: 64–100%) in a cluster randomised ‘ring vaccination’ trial.
The rVSVΔG-ZEBOV-GP candidate vaccine is recommended by the Strategic Advisory Group of Experts on Immunisation (SAGE) for use in Ebola outbreaks caused by the Zaire strain of the virus, in the event where there is no licensed vaccine. The vaccine had been administrated to more than 350 000 people in Guinea and in the 2018-2020 Ebola virus disease outbreaks in the Democratic Republic of the Congo under “expanded access” or “compassionate use” protocol. This vaccine was also used in the Ebola outbreak in Equateur in May-July 2018. In 2015, the vaccine was given to more than 16,000 volunteers involved in several studies in Africa, Europe and the United States where it was found to be safe and protective against the Ebola virus. More than 100,000 people have received the vaccine, by far the largest use of it since a trial in 2015 showed good efficacy. SAGE recommends vaccination of health care workers and frontline workers who may be in contact with Ebola patients.
For the protection of persons at highest risk of the Ebola outbreak, a ‘ring vaccination’ strategy is applied, which is similar to the approach used to eradicate smallpox. This strategy captures a social network of individuals and locations that may include dwellings or workplaces further afield, where the index patient spent time while symptomatic, or the households of individuals who had contact with the patient during the illness or after his or her death. Each ‘ring’ may be composed of an average of 150 persons:
i. Contacts, and contacts of contacts of confirmed Ebola virus disease patients (dead or alive),
ii. Health care and frontline workers (local and international) in the affected areas, and
iii. Health care and frontline workers in areas at risk of spread of the outbreak.
The rVSVΔG-ZEBOV-GP candidate vaccine was granted access to the Priority Medicine (PRIME) scheme by the European Medicine Agency (EMA), and Breakthrough Therapy designation by the US Food and Drug Administration (FDA). In November 2019, the European Commission granted a conditional marketing authorization to this vaccine (tradename “Ervebo”). In December 2020, the vaccine was approved and prequalified by WHO for use in individuals 18 years of age and older (except for pregnant and breastfeeding women) for protection against Ebola virus disease caused by Zaïre Ebola virus. The vaccine is a single dose vaccine regimen that has been found to be safe and protective against only the Zaire ebolavirus species of ebolavirus. This is the first approval of a vaccine for Ebola. A global stockpile of the Ervebo vaccine has become available starting January 2021.
Ad26.ZEBOV & MVA-BN-Filo (VAC52150) (Zabdeno and Mvabea)
This vaccine (Johnson & Johnson, & Janssen Vaccines & Prevention B.V, The Netherlands) is a prime/ boost candidate vaccine consisting of Ad26- and MVA-vectored components. It is a non replicative, recombinant adenovirus serotype 26 expressing envelope GP of Zaire Ebola virus species and modified vaccinia Ankara expressing 4 filoviruses nucleoproteins (GP for Zaire Ebola [Mayinga strain], Sudan Ebola, and Marburg viruses and nucleoprotein of Taï Forest Ebola virus). Two doses are required; an initial dose followed by a second “booster” dose 56 days later. This vaccine is also designed to protect against only the Zaire ebolavirus species of Ebola. In September 2019, the European Medicines Agency (EMA) granted an accelerated assessment and in November 2019, Janssen submitted a Marketing Authorization Application (MAA) to the EMA for approval. In May 2020, the EMA recommended granting a marketing authorization for the combination of Ad26.ZEBOV (Zabdeno) and MVA-BN-Filo (Mvabea) vaccines. The vaccine was approved for medical use in the European Union in July 2020.
A prime/boost candidate vaccine based on rVSV- and Ad5-vectored components (GamEvac-Combi) is registered Russia, its country of origin, based on Phase 2 data. It is a replicative, recombinant vesicular stomatitis virus and human adenovirus serotype 5 expressing envelope GP of Zaire (Makona strain) Ebola virus (prime & heterologous boost). The rVSVΔG-ZEBOV-GP candidate vaccine and (Ad26.ZEBOV/MVA-BNFilo) have been submitted for WHO Emergency Use Assessment and Listing (EUAL) documentation. More research is needed for the candidate vaccines, particularly on the duration of protection, and cross-protection against other species of Ebola virus and other filoviruses.
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- European Medicines Agency (EMA). (2020). New vaccine for prevention of Ebola virus disease recommended approval in the European Union. Press release 29 May 2020.
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- Merck. (2019). Merck’s Ervebo [Ebola Zaire Vaccine (rVSVΔG-ZEBOV-GP) live] Granted Conditional Approval in the European Union. Press release November 2019. Available at https://www.businesswire.com/news/home/20191111005601/en/Merck%E2%80%99s- ERVEBO%C2%AE-Ebola-Zaire-Vaccine-rVSV%CE%94G-ZEBOV-GP-live
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- WHO Fact Sheet: Ebola Virus Disease. Available at https://www.who.int/news-room/factsheets/detail/ebola-virus-disease. Accessed March 2019.
- Meeting of the Strategic Advisory Group of Experts on immunization, April 2017 – conclusions and recommendations. (2017). Wkly Epidemiol Rec., 92(22), 301–320.
- WHO Update With The Development Of Ebola Vaccines And Implications To Inform Future Policy Recommendations. Ebola vaccines – Background paper for SAGE deliberations. Available at https://www.who.int/immunization/sage/meetings/2017/april/1_Ebola_vaccine_background_document.pdf
- World Health Organization. (2019). WHO prequalifies Ebola vaccine, paving the way for its use in high-risk countries. Press release 12 November 2019. https://www.who.int/news/item/12-11-2019-who-prequalifies-ebola-vaccine-paving-the-way-for-its-use-in-highrisk-countries. Accessed October 2020