Use of Ebola Vaccines — Worldwide, 2021–2023

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
O. zairense, the virus responsible for Ebola, has caused the largest filovirus outbreaks worldwide; the average Ebola case fatality rate is approximately 50%. 1 Currently, 2 licensed vaccines are recommended for the prevention of Ebola caused by O. zairense: the 1-dose rVSVΔG-ZEBOV-GP (trade name ERVEBO [Merck]) and the 2-dose Ad26.ZEBOV and MVA-BN-Filo (trade name Zabdeno/Mvabea [Johnson & Johnson]). 2ERVEBO was licensed by the European Medicines Agency and the United States Food and Drug Administration in 2019 and is indicated for use in people aged >12 months. 2,3 e vaccine has also been approved in Burundi, Central African Republic, Congo, Côte d'Ivoire, Democratic Republic of the Congo (DRC), Ghana, Guinea, Rwanda, Sierra Leone, Uganda and Zambia (personal communication, Merck regulatory department, 6 December 2023). 2 In 2021, SAGE recommended use of ERVEBO in

Introduction
O. zairense, le virus responsable de la MVE, est à l'origine des plus importantes flambées épidémiques de filovirus dans le monde; le taux de létalité moyen de la MVE d'environ 50%. 1 À l'heure actuelle, 2 vaccins homologués sont recommandés pour la prévention de la maladie à virus Ebola causée par O. zairense: le vaccin à 1 dose rVSVΔG-ZEBOV-GP (nom commercial: ERVEBO  4 Zabdeno/Mvabea is recommended for preventive vaccination only in areas at lower risk for Ebola (or areas neighbouring an outbreak) because the full regimen requires 2 doses administered 56 days apart. 4VEBO was shown to be safe and effective during clinical trials and has probably played an important role in limiting morbidity and mortality during Ebola outbreaks since it was introduced. 2 In a study conducted in Ebola treatment facilities in the DRC, 56% of unvaccinated patients died from Ebola as compared with 25% of patients who were vaccinated before symptom onset. 5nsuring timely availability of Ebola vaccine doses in the event of a major Ebola outbreak is crucial to limiting the spread and protecting global health security.
In 2021, a global stockpile of ERVEBO was established under the ICG on vaccine provision to ensure equitable, timely access to vaccine doses for Ebola outbreaks. 6,7 en the ICG stockpile was established, it was agreed globally to maintain a stockpile of 500 000 doses. 7Gavi, the Vaccine Alliance (https://www.gavi.org)supports procurement of vaccine and the operational costs of vaccination to countries. 7Whereas the primary objective of the stockpile is to ensure the availability of doses for outbreak response, the ICG has approved requests for doses for targeted preventive vaccination of highrisk groups, including health-care and front-line workers in countries with previous Ebola outbreaks and their neighbours.This report describes use of Ebola vaccines and of the ICG vaccine stockpile during 2021-2023.

Methods
Data on past Ebola outbreaks were obtained from the weekly outbreak and emergency situation reports of the WHO Regional Office for Africa.Of the 11 requests to the ICG during this period, 10 were approved or partially approved and 1 was refused10 (Table 2).All the requests for outbreak response (3 of the 11) were delivered within 1 week of reception.Longer times to delivery were noted for shipments intended for preventive vaccination because of additional planning and engagement required for those activities.

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 (6570, 5% of doses shipped) reflects the smaller size and rapid containment of Ebola9 Person-to-person transmission of Ebola virus that persisted in immunologically privileged sites (sites that 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 transmission of virus from a nonhuman animal to humans. 10The request to the ICG that was not approved lacked justification that the security forces to be vaccinated were involved in Ebola outbreak response and were at risk.The ICG invited the country to resubmit the application prioritizing staff members involved in Ebola response activities.

Discussion
Le stock du GIC offre un accès équitable à des vaccins qui peuvent être expédiés rapidement en cas de flambée épidémique de MVE.Le nombre relativement faible de doses utilisées pour la riposte aux flambées épidémiques (6570, soit 5% des doses expédiées) reflète l'ampleur limitée et l'endiguement  a Doses approved by the International Coordinating Group moved from Equateur province to North Kivu province in DRC.-Doses transférées de la province de l'Équateur à la province du Nord-Kivu, en RDC, issues d'un précédent envoi de doses approuvé par le Groupe international de coordination.b Front-line workers are generally considered to be personnel directly involved in essential, public-facing roles related to health services or outbreak response; countries might define the group differently.-De manière générale, intervenants de première ligne s'entend du personnel directement impliqué dans des activités essentielles, en contact avec le public, liées aux services de santé ou à la riposte à une flambée épidémique; les pays peuvent définir ces intervenants de manière différente.
c This request lacked justification that the security forces to be vaccinated were involved in Ebola outbreak response and were at risk.The ICG invited the country to resubmit the application prioritizing staff members involved in Ebola response.-Cette demande ne présentait pas d'élément justifiant que les forces de sécurité à vacciner étaient impliquées dans la riposte à la flambée épidémique de MVE et qu'elles étaient exposées à un risque.Le Groupe international de coordination a invité le pays à soumettre de nouveau sa demande en donnant la priorité aux membres du personnel impliqués dans la riposte à la MVE.
outbreaks since 2021.North Kivu in DRC has received and administered more doses than any other geographical area worldwide since 2018, which may have contributed to the rapid containment of subsequent outbreaks in that area. 1 After approval by the ICG of use of the vaccine for prevention in 2022, WHO, in early 2023, circulated an internal memo on behalf of the ICG informing at-risk countries of the availability of vaccines for preventive vaccination of health-care and front-line workers.Preventive vaccination campaigns have targeted these workers in at-risk countries, as they are at increased risk of exposure due to their frequent contact with patients.11It is estimated that addition of preventive Ebola vaccination of these workers could reduce the total numbers of cases, hospitalizations and deaths in Ebola outbreaks by 14-38% over those seen with nonpharmaceutical interventions and ring vaccination alone. 11 Variations in the size and time to containment of Ebola outbreak makes it difficult to predict future vaccine needs.Repurposing doses for preventive vaccination of targeted groups can both protect high-risk people and make use of doses with a shorter shelf life.Over 200 000 short-shelf-life doses in the ICG stockpile that are due to expire in 2024 could be redirected for preventive vaccination.In addition to reactive (outbreak response) vaccination, early planning for preventive vaccination with short-shelf-life doses could be included in future stockpile management strategies.Additional studies to account for variations in outbreak size would guide planning to maximize the cost-efficiency of stockpile management.
The frequency of recent outbreaks, especially those linked to viral persistence, indicates that innovative strategies are required to protect Ebola survivors and prevent reintroduction.One such strategy is offering post-outbreak vaccination to close contacts of survivors, including new sex partners and other groups at risk for transmission because of viral persistence.12Additional avenues to extend preventive vaccination of high-risk populations could be explored in countries at risk for outbreaks.Demand-generating activities13 based on findings from studies of community engagement and vaccine acceptance in target risk groups could be included in vaccination campaigns and in targeted engagement plans.Investments and advocacy for preventive vaccination against Ebola are crucial for health system preparedness and resilience.Currently,

Limitations
The findings reported are subject to at least 2 limitations.First, whereas the Ebola vaccine has reduced morbidity and mortality during outbreaks, their impact on preventing outbreaks is difficult to ascertain because of the infrequent occurrence of the disease.Secondly, important data are lacking on the duration of protection, effectiveness in outbreak situations and whether booster doses will be required.These data will be necessary to guide decisions on vaccination strategies and should be addressed in future research.

Implications for public health practice
The availability of licensed Ebola vaccines is an important advance 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 on preventive vaccination are crucial for health system preparedness and resilience.Priority should be given to working with at-risk countries to identify high-risk groups and generate demand for preventive vaccination to optimize use of the stockpile.
Ensuring the availability of sufficient Ebola vaccine doses for emergency outbreak response remains the priority of the ICG stockpile.
Author affiliations

Affiliations des auteurs
14 Ensemble de questions et d'activités de recherche prioritaires sur la mise en oeuvre des vaccins pour guider la génération de données probantes et la prise de décisions concernant les vaccins contre le virus Ebola.
1Information on requests and deliveries from the Ebola vaccine stockpile during 2021-2023 was obtained from the ICG.Data on the stockpile size were obtained from UNICEF Supply Division's ICG Ebola vaccine stockpile report dated 19 January 2024. 8scriptive analysis of data was conducted in Microsoft Excel.The activity was reviewed by the United States Centers for DiseaseResultsEbola 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 outbreak in eastern DRC in 2018-2020.Since 2015, when Ebola vaccines were first used in outbreak response, recorded Ebola outbreaks have varied in frequency, size, and origin, with recent outbreaks more often linked to reintroduction through viral persistence 9 (4 of 5 outbreaks since 2021) than to zoonotic spillover (Table1).
santé et les intervenants de première ligne, dans des pays qui ont connu des épidémies de MVE par le passé et les pays limitrophes.Le présent rapport décrit l'utilisation des vaccins contre le virus Ebola et le rôle du stock de vaccins du GIC au cours de la période 2021-2023.MéthodesLes données sur les flambées épidémiques de MVE proviennent des rapports de situation hebdomadaires sur les flambées épidémiques et les situations d'urgence publiés par le Bureau régional de l'OMS pour l'Afrique. 1Les informations sur les demandes de vaccins contre le virus Ebola provenant du stock du GIC et les livraisons de vaccins au cours de la période 2021-2023 ont été obtenues auprès du GIC.Les données sur la taille du stock proviennent du rapport de la Division des approvisionnements de l'UNICEF sur le stock de vaccins contre le virus Ebola du GIC daté du 19 janvier 2024. 8Une analyse descriptive Control and Prevention (CDC), deemed not to be research and conducted consistent with applicable federal law and CDC policy.The ICG Ebola vaccine stockpile reached the goal of 500 000 doses in 2022.As of December 2023, it held 518 890 doses.A total of 208 390 (40%) doses in the current stockpile are scheduled to expire in 2024.Doses from the ICG stockpile were first used in 2021 in DRC for outbreak response.During 2021-2023, 145 690 ERVEBO doses were shipped from the stockpile to meet requests.
a b Zoonotic spillover, transmission of a virus from a non-human animal to a human.-Latransmission zoonotique est la transmission d'un virus d'un animal non humain à un humain.cPerson-to-person transmission of Ebola virus from virus that persisted in immunologically privileged sites (sites that tolerate 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.-Transmission interhumaine du virus Ebola ayant persisté dans des sites privilégiés sur le plan immunologique (sites capables de tolérer l'introduction de l'antigène sans provoquer de réponse immunitaire inflammatoire, notamment les yeux, le placenta, le foetus, les testicules et le système nerveux central) ou dans des liquides biologiques après la guérison d'une infection aiguë.

Table 2
Requests to the ICG on vaccine provision for Ebola vaccine deliveries from the global stockpile, by country and year -worldwide, 2021-2023 Tableau 2 Demandes soumises au Groupe international de coordination pour l'approvisionnement en vaccins pour la livraison de vaccins contre le virus Ebola provenant du stock mondial, par pays et par année -monde entier, 2021-2023 Activities to increase public awareness of and coverage with the vaccine, which might include public education campaigns, health-care worker education and engagement, community outreach, targeted messaging to high-risk groups and increasing access to the vaccine.rapidedesflambées de MVE depuis 2021.Le Nord-Kivu (RDC) a reçu et administré plus de doses que toute autre zone géographique dans le monde depuis 2018, ce qui pourrait avoir contribué à la maîtrise rapide des flambées ultérieures dans cette zone. 1 À la suite de l'approbation du vaccin à usage préventif par le GIC en 2022, l'OMS a diffusé, début 2023, une note interne au nom du GIC informant les pays à risque de la disponibilité de doses pour la vaccination préventive des agents de santé et des intervenants de première ligne, qui courent un risque accru en raison de leurs contacts fréquents avec les patients. 11n estime que l'ajout de la vaccination préventive contre le virus Ebola de ces agents et intervenants pourrait réduire de 14% à 38% le nombre total de cas, d'hospitalisations et de décès lors de flambées épidémiques de MVE par rapport aux interventions non pharmaceutiques et à la vaccination en anneau seules. 11es variations observées dans l'envergure des flambées épidémiques de MVE et dans le temps nécessaire pour les endiguer rendent difficile la prévision des besoins futurs en termes de vaccins.La réaffectation des doses pour la vaccination préventive de groupes cibles peut protéger les personnes à haut risque et permet d'utiliser des doses dont la date de péremption approche.Plus de 200 000 doses du stock du GIC qui seront périmées en 2024 pourraient être redirigées vers la vaccination préventive.En plus de mettre l'accent sur la vaccination réactive (riposte à une flambée épidémique), la planification précoce de la vaccination préventive avec des doses dont la date de péremption approche pourrait être intégrée dans les futures stratégies de gestion du stock.Des études supplémentaires qui tiennent compte des variations de l'ampleur des flambées épidémiques permettraient de guider la planification afin de maximiser le rapport coût-efficacité de la gestion du stock. 13 et le plaidoyer en faveur de la vaccination préventive contre la MVE sont cruciaux pour la préparation et la résilience des systèmes de santé.À l'heure actuelle, Gavi, l'OMS et l'UNICEF travaillent de concert avec d'autres partenaires pour élaborer un programme d'apprentissage 14 afin d'éclairer les priorités de la recherche et les décisions de financement concernant l'utilisation des vaccins contre le virus Ebola.