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The Front Page of Medicine

Infectious Disease · 2017

Ervebo (rVSV-ZEBOV) Ebola Vaccine: Ebola Ça Suffit! Ring Vaccination Trial

Ebola Ça Suffit! (Ebola, that's enough!) ring vaccination trial; rVSV-ZEBOV = recombinant vesicular stomatitis virus Zaire Ebolavirus vaccine

Electron micrograph of Ebola virus, the pathogen targeted by the rVSV-ZEBOV (Ervebo) vaccine
CDC/ Dr. Frederick A. Murphy / Public domain (Wikimedia Commons)

The 2014 to 2016 West Africa Ebola outbreak killed more than 11,000 people across Guinea, Liberia, and Sierra Leone, exposing the near-total absence of licensed vaccines or therapeutics for filovirus disease. Experimental vaccine candidates had been in preclinical development for years, primarily in response to biosecurity concerns rather than public health investment in endemic regions. When the outbreak began, rVSV-ZEBOV, a recombinant vesicular stomatitis virus engineered to express the Ebola Zaire surface glycoprotein, had been developed with Canadian government funding and was held by Merck. It had never been tested in a phase 3 efficacy trial in humans.

With transmission ongoing in Guinea in mid-2015, a consortium led by Ana Maria Henao-Restrepo of the World Health Organization designed a ring vaccination trial. The strategy, borrowed from the smallpox eradication campaigns of the 1970s, involved identifying every known contact and contact-of-contact of a confirmed Ebola case and vaccinating them as a cluster. Individual randomization was ruled out on both logistical and ethical grounds; instead, clusters were randomized to immediate or 21-day delayed vaccination. The trial enrolled at sites in the Boke, Coyah, and Forecariah prefectures of Guinea.

Among 3,537 individuals in immediately vaccinated clusters, zero Ebola cases occurred beginning 10 days after vaccination. In the delayed vaccination clusters, 16 cases were recorded during the waiting period. The 10-day latency was built into the analysis to allow for the vaccine's incubation effect. John Edmunds at the London School of Hygiene and Tropical Medicine contributed to study design and data analysis, helping to calculate that the trial had achieved an estimated efficacy of 100% in the immediately vaccinated clusters, with confidence intervals excluding zero. The delayed arm was subsequently offered immediate vaccination, eliminating the control comparison but protecting participants.

The FDA granted approval under the brand name Ervebo in December 2019, making it the first licensed Ebola vaccine. The platform was notable for its speed: a live attenuated recombinant viral vector could be manufactured and scaled more rapidly than inactivated or subunit vaccines, a property that influenced discussions about rapid-response vaccine design for future outbreak pathogens. The vaccine requires cold chain storage at minus 60 to minus 80 degrees Celsius, a logistical constraint that shaped deployment strategies in subsequent outbreaks.

During the 2018 to 2020 Kivu outbreak in the Democratic Republic of Congo, more than 300,000 doses of Ervebo were administered using ring vaccination and geographic targeting. The outbreak eventually caused more than 2,200 deaths, prolonged by active conflict and community distrust rather than vaccine failure. The infrastructure and supply chain relationships built during the Guinea trial and the DRC response directly informed the deployment protocols used in later outbreaks. A two-dose heterologous prime-boost regimen combining rVSV-ZEBOV with an adenoviral vector was also developed for populations at ongoing endemic risk.

Key People

Read the original — PubMed

Lancet. 2017;389(10068):505-518

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