Use of Ebola Vaccines — Worldwide, 2021–2023
Weekly / April 25, 2024 / 73(16);360–364
Ruth Kallay, MPH1; Reena H. Doshi, PhD2; Pierre Muhoza, PhD1; Mary J. Choi, MD3; Anaïs Legand, MPH4; Emma Aberle-Grasse1; Aminata Bagayoko, MD4; Terri B. Hyde, MD1; Pierre Formenty, DVM4; Alejandro Costa, MSc4 (View author affiliations)
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What is already known about this topic?
The International Coordinating Group on Vaccine Provision established an Ebola vaccine stockpile in 2021 to ensure equitable, rapid access to vaccines during an outbreak.
What is added by this report?
Since 2021, the absence of large Ebola virus disease (Ebola) outbreaks has resulted in fewer vaccine doses being used for outbreak response. Out of the 145,690 doses shipped from the stockpile through 2023, 95% (139,120) have been repurposed for preventive vaccination, and 5% (6,570) were used in outbreak response.
What are the implications for public health practice?
Repurposing doses for preventive vaccination could be prioritized in the absence of Ebola outbreaks to prevent transmission and maximize the cost-efficiency and benefits of the stockpile.
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Abstract
Ebola virus disease (Ebola) is a rare but severe illness in humans, with an average case fatality rate of approximately 50%. Two licensed vaccines are currently available against Orthoebolavirus zairense, the virus that causes Ebola: the 1-dose rVSVΔG-ZEBOV-GP (ERVEBO [Merck]) and the 2-dose regimen of Ad26.ZEBOV and MVA-BN-Filo (Zabdeno/Mvabea [Johnson & Johnson]). The Strategic Advisory Group of Experts on Immunization recommends the use of 1-dose ERVEBO during Ebola outbreaks, and in 2021, a global stockpile of ERVEBO was established to ensure equitable, timely, and targeted access to vaccine doses for future Ebola outbreaks. This report describes the use of Ebola vaccines and the role of the stockpile developed and managed by the International Coordinating Group (ICG) on Vaccine Provision during 2021–2023. A total of 145,690 doses have been shipped from the ICG stockpile since 2021. However, because outbreaks since 2021 have been limited and rapidly contained, most doses (139,120; 95%) shipped from the ICG stockpile have been repurposed for preventive vaccination of high-risk groups, compared with 6,570 (5%) used for outbreak response. Repurposing doses for preventive vaccination could be prioritized in the absence of Ebola outbreaks to prevent transmission and maximize the cost-efficiency and benefits of the stockpile.
Introduction
Orthoebolavirus zairense, the virus responsible for Ebola virus disease (Ebola), has caused the largest filovirus outbreaks worldwide; the average Ebola case fatality rate is approximately 50% (1). Currently, two licensed vaccines are recommended for the prevention of Ebola caused by Orthoebolavirus zairense: the 1-dose rVSVΔG-ZEBOV-GP (ERVEBO [Merck]) and the 2-dose Ad26.ZEBOV and MVA-BN-Filo (Zabdeno/Mvabea [Johnson & Johnson]) (2). ERVEBO was licensed by the European Medicines Agency and the Food and Drug Administration in 2019 and is indicated for use in persons aged >12 months (2,3). It has a shelf life of 3 years. The vaccine has also been approved in Burundi, Central African Republic, Côte d’Ivoire, Democratic Republic of the Congo (DRC), Ghana, Guinea, Republic of the Congo, Rwanda, Sierra Leone, Uganda, and Zambia (Merck regulatory department, personal communication, December 6, 2023) (2). In 2021, the Strategic Advisory Group of Experts on Immunization recommended using ERVEBO in ring vaccination during Ebola outbreaks, because it confers protection after 1 dose (4). Zabdeno/Mvabea is recommended for preventive vaccination in areas at lower risk for Ebola (or areas neighboring an outbreak) because the full regimen requires 2 doses administered 56 days apart (4).
ERVEBO was shown to be safe and effective during clinical trials and has likely played an important role in limiting Ebola morbidity and mortality during outbreaks since it was first introduced (2). In a study conducted in Ebola treatment facilities in DRC, 56% of unvaccinated patients died from Ebola, compared with 25% of patients vaccinated before symptom onset (5). Ensuring timely availability of Ebola vaccine doses in the event of a major Ebola outbreak is crucial to limiting its spread and protecting global health security.
In 2021, a global stockpile of ERVEBO was established under the International Coordinating Group (ICG) on Vaccine Provision to ensure equitable and timely access to vaccine doses for Ebola outbreaks* (6). Upon the establishment of the ICG stockpile, the global agreement was to maintain the stockpile at 500,000 doses (6). Gavi, the Vaccine Alliance (https://www.gavi.org), supports the procurement of vaccine and operational costs to countries for vaccination (6). Whereas the availability of doses for outbreak response is the primary objective of the stockpile, ICG has approved requests for targeted preventive vaccination of high-risk groups, including health care workers and frontline workers in countries at risk for Ebola outbreaks. This report describes the use of Ebola vaccines and the role of the ICG vaccine stockpile during 2021–2023.
Methods
Data on past Ebola outbreaks were obtained from the World Health Organization (WHO) Regional Office for Africa’s weekly Outbreak and Emergencies situation reports (1). Information on Ebola vaccine stockpile requests and deliveries during 2021–2023 was obtained from the ICG Secretariat. Data on the stockpile size were obtained from UNICEF Supply Division’s ICG Ebola vaccine stockpile report dated January 19, 2024 (7). This activity was reviewed by CDC, deemed not research, and was conducted consistent with applicable federal law and CDC policy.†
Results
Ebola vaccine was first used during clinical trials in the 2014–2015 West African outbreak, then under a compassionate use protocol in Guinea during 2015, and again in the 2018–2020 eastern DRC outbreak. Since 2015, when Ebola vaccines were first deployed in outbreak response, recorded Ebola outbreaks have varied in frequency, size, and origin, with recent outbreaks more often linked to reintroduction through viral persistence§ (four of five outbreaks since 2021) than to zoonotic spillover (Table 1).
The ICG Ebola vaccine stockpile reached the goal of 500,000 doses in 2022 and, as of December 2023, holds 518,890 doses. In total, 208,390 (40%) doses from the current stockpile are scheduled to expire in 2024. Doses from the ICG stockpile were first deployed in 2021 in DRC for outbreak response. During 2021–2023, a total of 145,690 ERVEBO doses were shipped through requests from the ICG stockpile. Among 11 requests to ICG during this period, 10 were approved or partially approved, and one request was declined¶ (Table 2). All requests to ICG for outbreak response (three of 11) were delivered within 1 week of being received. Longer times to delivery were noted for shipments intended for preventive vaccination because of the additional planning and engagement around those activities.
The number of doses shipped from the stockpile has increased annually, from 4,800 doses in 2021, to 13,870 doses in 2022, and 127,020 doses in 2023. During this period, 42,620 doses expired. Most doses shipped (139,120; 95%) were repurposed for preventive vaccination. Five percent (6,570) of doses were shipped for outbreak response use. DRC has received the largest number of vaccine doses (111,000; 76%), followed by Uganda (23,460; 16%) and Guinea-Bissau (11,170; 8%).
Discussion
The ICG stockpile provides equitable access to vaccines that can be shipped quickly in the event of an Ebola outbreak. The relatively small number of doses used for outbreak response (6,570; 5% of doses shipped) reflects the smaller size and rapid containment of Ebola outbreaks since 2021. North Kivu, DRC, has received and administered more doses than any other geographic area worldwide since 2018, which might have contributed to the rapid containment of subsequent outbreaks in that area (1).
After approvals of vaccine for preventive use by ICG in 2022, WHO, in early 2023, circulated an internal memo on behalf of ICG informing at-risk countries of the availability of vaccines for preventive vaccination of health care workers and frontline workers. Preventive vaccination campaigns have targeted health care workers and frontline workers in at-risk countries, given their increased risk for exposure because of their frequent contact with patients (8). The addition of preventive Ebola vaccination of these workers could reduce total cases, hospitalizations, and deaths in Ebola outbreaks by an estimated 14%–38% compared with nonpharmaceutical interventions and ring vaccination alone (8).
The variability of Ebola outbreak size and time to containment makes predicting future vaccine needs challenging. Repurposing doses for preventive vaccination of targeted groups can protect high-risk persons as well as make use of doses with a shorter shelf life. More than 200,000 short–shelf-life doses in the ICG stockpile due to expire in 2024 could be redirected for preventive vaccination. In addition to focusing on reactive (outbreak response) vaccination, early planning for preventive vaccination with short–shelf-life doses could be incorporated into future stockpile management strategies. Additional studies accounting for the variability in outbreak size could guide planning to maximize the cost-efficiency of stockpile management.
The frequency of recent outbreaks, especially those linked to viral persistence, highlights the need for innovative strategies to protect Ebola survivors and prevent reintroductions. One such strategy is to offer postoutbreak immunization to close contacts of survivors, including new sex partners and other groups at risk for transmission because of viral persistence (9). Additional avenues to expand preventive vaccination among high-risk populations could be explored in countries at risk for outbreaks. Demand-generation activities** incorporating findings from community engagement and vaccine acceptance studies in targeted risk groups could accompany vaccination campaigns and help develop targeted engagement plans. Investments and advocacy for preventive vaccination against Ebola are crucial for health system preparedness and resiliency. Currently, Gavi, WHO, and UNICEF are coordinating with other partners to develop a learning agenda†† to help guide research prioritization and funding decisions for Ebola vaccine use.
Limitations
The findings in this report are subject to at least two limitations. First, whereas the Ebola vaccine has reduced morbidity and mortality during outbreaks, the impact of Ebola vaccines on preventing outbreaks is difficult to ascertain because of the infrequent occurrence of the disease. Second, important data are lacking regarding the duration of protection, vaccine effectiveness in outbreak situations, and the need for booster doses. These data will be needed to guide decision-making regarding vaccination strategies and should be a focus for future research.
Implications for Public Health Practice
The availability of licensed Ebola vaccines is an important advancement in Ebola prevention and global health security. In the absence of large-scale outbreaks, the demand for vaccines lags behind the current supply of doses, and preventive vaccination could be considered for high-risk groups. Investments, advocacy, and additional research to inform preventive vaccination are crucial for health system preparedness and resiliency. Focus on working with countries at risk for Ebola outbreaks to identify high-risk groups and generate demand for preventive vaccination is important for optimizing the use of the stockpile. Ensuring the availability of sufficient Ebola vaccine doses for emergency outbreak response remains the priority of ICG.
Corresponding author: Ruth Kallay, rkallay@cdc.gov.
1Global Immunization Division, Global Health Center, CDC; 2Emergency Preparedness and Response, World Health Organization Regional Office for Africa, Brazzaville, Republic of the Congo; 3Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, CDC; 4Viral Hemorrhagic Fevers team, Health Emergencies Programme, World Health Organization, Geneva, Switzerland.
All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.
* The ICG Ebola vaccine stockpile is managed by the ICG on Vaccine Provision comprising Médecins sans Frontières, the International Federation of Red Cross and Red Crescent Societies, UNICEF, and the World Health Organization. These organizations support maintenance and decisions regarding vaccine allocations from the ICG on Vaccine Provision’s stockpile of Ebola vaccine. https://www.who.int/groups/icg/about
† 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.
§ Person-to-person transmission of Ebola virus that persisted in immunologically privileged sites (sites that are able to tolerate the introduction of antigen without eliciting an inflammatory immune response, including the eyes, placenta, fetus, testicles, and central nervous system) or body fluids after recovery from acute infection in humans, in contrast to outbreaks originating from zoonotic spillover, which is the transmission of virus from an animal to a human.
¶ The request to ICG that was not approved lacked justification that the security forces to be vaccinated were involved in Ebola outbreak response and were at risk. ICG invited the country to resubmit the application prioritizing staff members involved in Ebola response activities.
** Activities that aim to increase public awareness of and coverage with the vaccine and might include public education campaigns, health care worker education and engagement, community outreach, targeted messaging to high-risk groups, and increased access to the vaccine.
†† A set of prioritized vaccine implementation research questions and activities to guide evidence-building and decision-making around the Ebola vaccine.
References
- World Health Organization Regional Office for Africa. Outbreaks and Emergencies Bulletin. Cité du Djoué, Brazzaville, Republic of the Congo: World Health Organization Regional Office for Africa; 2024. https://www.afro.who.int/health-topics/disease-outbreaks/outbreaks-and-other-emergencies-updates?page=0
- World Health Organization. Ebola virus disease vaccines. Geneva, Switzerland: World Health Organization; 2023. https://www.who.int/news-room/questions-and-answers/item/ebola-vaccines
- Merck. U.S. FDA approves Merck’s ERVEBO (Ebola Zaire Vaccine, Live) for use in children 12 months of age and older. [Press release]. Rahway, NJ: Merck; 2023. https://www.merck.com/news/u-s-fda-approves-mercks-ervebo-ebola-zaire-vaccine-live-for-use-in-children-12-months-of-age-and-older/
- World Health Organization. Meeting of the Strategic Advisory Group of Experts on Immunization, 22–24 March 2021: conclusions and recommendations. Geneva, Switzerland: World Health Organization; 2021. https://www.who.int/publications/i/item/meeting-of-the-strategic-advisory-group-of-experts-on-immunization-22-24-march-2021-conclusions-and-recommendations
- Coulborn RM, Bastard M, Peyraud N, et al. Case fatality risk among individuals vaccinated with rVSVΔG-ZEBOV-GP: a retrospective cohort analysis of patients with confirmed Ebola virus disease in the Democratic Republic of the Congo. Lancet Infect Dis 2024. Epub February 7, 2024. https://doi.org/10.1016/S1473-3099(23)00819-8 PMID:38340736
- Gavi, The Vaccine Alliance. 500,000 doses of Ebola vaccine to be made available to countries for outbreak response. Geneva, Switzerland: Gavi, The Vaccine Alliance; 2021. https://www.gavi.org/news/media-room/500000-doses-ebola-vaccine-be-made-available-countries-outbreak-response
- UNICEF. Emergency stockpile availability report – Ebola vaccine. New York, NY: UNICEF; 2024. https://www.unicef.org/supply/documents/emergency-stockpile-availability-report-ebola-vaccine
- Bisanzio D, Davis AE, Talbird SE, et al. Targeted preventive vaccination campaigns to reduce Ebola outbreaks: an individual-based modeling study. Vaccine 2023;41:684–93. https://doi.org/10.1016/j.vaccine.2022.11.036 PMID:36526505
- Doshi RH, Fleming M, Mukoka AK, et al. Vaccination of contacts of Ebola virus disease survivors to prevent further transmission. Lancet Glob Health 2020;8:e1455–6. https://doi.org/10.1016/S2214-109X(20)30454-X PMID:33220205
Abbreviations: CFR = case fatality rate; DRC = Democratic Republic of the Congo; NA = not applicable.
* Outbreak data obtained from the World Health Organization Regional Office for Africa weekly Outbreak and Emergencies situation reports was compared with data from CDC available online. https://www.cdc.gov/vhf/ebola/history/chronology.html (Accessed January 9, 2024).
† Zoonotic spillover is the transmission of virus from an animal to a human.
§ Person-to-person transmission of Ebola virus from virus that persisted in immunologically privileged sites (sites that are able to tolerate the introduction of antigen without eliciting an inflammatory immune response, including the eyes, placenta, fetus, testicles, and central nervous system) or body fluids after recovery from acute infection.
Abbreviations: DRC = Democratic Republic of the Congo; ICG = International Coordinating Group; NA = not applicable.
* Doses shifted from Equateur province to North Kivu province in DRC from previously shipped doses approved by ICG.
† Frontline workers are generally considered to be personnel directly involved in essential, public-facing roles related to health services or outbreak response; countries might define this group differently.
§ The request to ICG that was not approved lacked justification that the security forces to be vaccinated were involved in Ebola outbreak response and were at risk. ICG invited the country to resubmit the application prioritizing staff members involved in Ebola response activities.
Suggested citation for this article: Kallay R, Doshi RH, Muhoza P, et al. Use of Ebola Vaccines — Worldwide, 2021–2023. MMWR Morb Mortal Wkly Rep 2024;73:360–364. DOI: http://dx.doi.org/10.15585/mmwr.mm7316a1.
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