Ervebo® (rVSVΔG-ZEBOV-GP) Ebola Vaccine May 2023
Merck's Ervebo® Ebola Vaccine (rVSV-ZEBOV-GP, rVSV-ZEBOV, v920) is a live, recombinant, replication-competent vaccine. Ervebo's active ingredient is Vesicular Stomatitis Virus (VSV), in which its surface protein has been replaced with that of ebola virus disease (EBOV). In addition, this Ebola vaccine was genetically engineered to express the main glycoprotein from the Zaire ebolavirus to provoke a neutralizing immune response.
The Joint Project Manager for Chemical, Biological, Radiological, and Nuclear Medical (JPM-CBRN) helped provide a test that enabled Merck Sharp & Dohme B.V. to test human and non-human primate samples. The Ervebo vaccine protects people from Zaire Ebolavirus but not against other species of Ebolavirus or Marburgvirus. In addition, it is improbable people could become infected with EBOV from the Ervebo vaccine because it only contains one gene from the Ebola virus, not the whole virus. Specifically, it includes a gene for the EBOV glycoprotein that replaces the gene for the native VSV glycoprotein, says the U.S. Centers for Disease Control and Prevention (CDC).
The first Ebola vaccine was authorized by the European Medicines Agency (EMA) for the European Union on November 11, 2021 - (EMEA/H/C/004554) and was Listed by the World Health Organization (WHO). In addition, it was licensed by the U.S. Food and Drug Administration (FDA) to prevent EVD in individuals 18 and older in December 2019. And was then authorized for use in Canada. Since the Ervebo vaccination program began in central Africa in 2019, approximately 300,000 persons have been vaccinated with the ERVEBO vaccine.
As of March 8, 2022, the U.S. CDC stated, 'The correlate of protection, or the specific immune response to the ERVEBO vaccine that closely relates to protection against infection with EBOV, is unknown and still being studied. It is also unknown whether it is effective when administered concurrently with antiviral medication, immune globulin, and/or blood or plasma transfusion. And the duration of protection conferred by an initial dose of ERVEBO is also unknown. Furthermore, a booster dose for people who have been previously vaccinated may extend the duration of protection for ERVEBO. Therefore, scientists continue to monitor people who have received the vaccine to learn more.'
Current evidence shows that the ERVEBO vaccine is highly effective against the Zaire ebolavirus but does not provide cross-protection against the Sudan ebolavirus or Marburgvirus. On December 14, 2022, the NEJM published an Original Article that confirmed the ERVEDO vaccine's safety and effectiveness.
Drugbank's Accession Number: DB15595. ATC code: J07BX02. STN: 125690. Clinical Reviewer: Rebecca Reindel.
New Jersey-based Merck & Co. Inc. licensed the global R&D and manufacturing rights from Newlink Genetics Corp.'s phase I Ebola vaccine in 2014. The Public Health Agency of Canada, which initially developed the vaccine, retained noncommercial rights in the agreement.
Ervebo Price
This UNICEF table shows awarded price per dose, product, supplier, and calendar year, based on a multi-year supply agreement. Additional Ebola vaccine price information is available at InstantRx™.
Ervebo Availability May 2023
As of May 2023, the Ervebo vaccine is recommended by U.S. CDC for adults at high risk for potential exposure to the Ebola Zaire virus. The Ervebo vaccine is not planned for commercial marketing in the U.S. but is maintained in the U.S. Strategic National Stockpile (SNS), with access facilitated by the U.S. government. Licensed healthcare providers interested in initial doses of ERVEBO for patients that meet the eligibility criteria should email [email protected] with the subject line: Request for ERVEBO.
Ervebo Ingredients
This Ebola vaccine's inactive ingredients include recombinant human serum albumin and tromethamine (Tris) buffer, which contains a trace amount of rice protein.
Ervebo Indication
The Ervebo vaccine is indicated to prevent disease caused by Zaire ebolavirus in individuals 18 years of age and older. However, the duration of protection conferred by Ervebo is unknown. In addition, when administered concurrently with antiviral medication, the vaccine's effectiveness, immune globulin, and/or blood or plasma transfusions are unknown.
Following vaccination with the Ervebo vaccine, individuals may test positive for anti-Ebola glycoprotein (GP) antibody and/or Ebola GP nucleic acid or antigens. However, GP-based testing may have limited diagnostic value during vaccine viremia, in the presence of vaccine-derived Ebola GP, and following antibody response to the vaccine. Therefore, the CDC says that a polymerase chain reaction is one of the most commonly used diagnostic methods because of its ability to detect ebola virus disease.
The WHO published the revised Ebola Vaccine FAQ, and the U.S. CDC published 'Ebola Vaccine: Information for U.S. Healthcare Providers.'
Ervebo Efficacy
The CDC evaluated vaccine efficacy in a two-part phase 3, open-label, cluster-randomized, controlled ring vaccination trial in Guinea during the 2014–2016 Ebola outbreak in West Africa. In the initial study, clusters of confirmed EVD patients and contacts were offered immediate vaccination or delayed vaccination (21 days after randomization). The primary outcome of interest was the incidence of laboratory-confirmed EVD with onset ≥10 days after randomization. The ten days were selected to account for the incubation period of EVD and the unknown length of time from vaccination to protective immunity development. Based on cluster-level data, vaccine efficacy in the follow-up study was calculated to be 100% (95% CI: 79.3%–100%).
Ervebo Dosage
The Ervebo vaccine is administered as a single-dose intramuscular injection. You will get this vaccine as an injection at the top of your arm. However, Merck says, 'do not administer Ervebo to individuals with a severe allergic reaction (e.g., anaphylaxis) to any vaccine component, including rice protein.' This is because the safety and effectiveness of Ervebo have not been assessed in immunocompromised individuals.
There are no adequate and well-controlled studies of Ervebo in pregnant women. Human data from clinical trials with Ervebo are insufficient to establish the presence or absence of vaccine-associated risk during pregnancy. Therefore, the decision to vaccinate a pregnant woman should consider the woman's risk of exposure to Zaire ebolavirus. Furthermore, previous clinical studies of Ervebo with seniors did not include sufficient numbers of subjects 65 and older to determine whether they respond differently from younger subjects.
Ervebo Booster Dose
FDA approves initial doses of ERVEBO for the prevention of EVD. However, the duration of protection given by an initial ERVEBO dose is unknown. Since the booster dose is not an FDA-approved indication for ERVEBO, the CDC sponsored an expanded access IND protocol for booster dose administration.
INO-4201 Booster Dose
A Phase 1b clinical trial evaluating a DNA vaccine candidate INO-4201 as a booster in healthy adult participants who previously received a single injection of Ervebo was well-tolerated and boosted humoral responses in 100% (36 of 36) of treated participants.
Ervebo Side Effects
Injection-site side events include injection-site pain, swelling, and redness. The most common injection-site adverse events were injection-site pain (70%), swelling (17%), and redness(12%). The most common systemic adverse events reported following vaccination with ERVEBO were headache (37%), feverishness (34%), muscle pain (33%), fatigue (19%), joint pain (18%), nausea (8%), arthritis (5%), rash (4%) and abnormal sweating (3%).
Overall, the CDC states the pregnancy loss rate among pregnant women who received immediate vaccination was not statistically significantly higher than that among unvaccinated pregnant women. In addition, no external congenital anomalies were detected among live-born infants in either group (n = 44).
Tell your healthcare provider promptly about any unusual or severe symptoms after receiving this vaccine. You may also report any side effects to Merck Sharp & Dohme Corp, a Merck & Co., Inc. subsidiary, at 1-877-888-4231 or directly to Vaccine Adverse Event Reporting System (VAERS). The VAERS toll-free number is 1-800-822-7967, or report online to www.vaers.hhs.gov.
Ervebo Pregnant Women
Among immediately vaccinated pregnant women, 14 of 31 (45%) experienced pregnancy loss compared with 11 of 33 (33%) unvaccinated pregnant women (unadjusted RR: 1.35; 95% CI: 0.73–2.52). Overall, the pregnancy loss rate among pregnant women who received immediate vaccination was not statistically significantly higher than that among unvaccinated pregnant women. In addition, no external congenital anomalies were detected among live-born infants in either group (n = 44).
International Coordinating Group on Vaccine Provision - Ebola Vaccine Stockpile
The ICG manages the Ebola vaccine's global stockpile, created as an additional tool to help control Ebola outbreaks. Ebola outbreaks are relatively rare and unpredictable. Due to limited vaccine quantities, the current Ervebo vaccine is reserved for outbreak response to protect people at the highest risk of contracting Ebola – including health care and frontline workers in an outbreak under a ring vaccination strategy. An initial 6,890 doses will be made available on a priority basis for outbreak response starting January 12, 2021.
Depending on the rate of vaccine deployment, it could take 2 to 3 years to reach the SAGE-recommended level of 500,000 doses for emergency stockpiles of vaccines. WHO, UNICEF, Gavi, and vaccine manufacturers continuously assess options to increase vaccine supply if global demand increases.
Ervebo U.S. CDC - FDA Presentations
The U.S. CDC published an update to the VIS sheet on June 30, 2022. On November 3, 2021, Jason Malenfant, MD, MPH, Epidemic Intelligence Service Officer Viral Special Pathogens Branch CDC, presented 'Evidence for Expansion of Recommendations for PreExposure Vaccination with rVSVΔG-ZEBOV-GP Ebola Vaccine for Special Pathogens Treatment Centers and Laboratory Response Network Facilities.' In addition, Wilbur Chen, MD, University of Maryland School of Medicine Chair, Ebola Vaccine Working Group, presented an Overview. And Caitlin Cossaboom, DVM, Ph.D., MPH, presented Policy Questions.
The U.S. FDA granted a Priority Review and a Tropical Disease Priority Review Voucher on September 17, 2019. The FDA also granted Breakthrough Therapy designation for Ervebo to facilitate the vaccine's development and scientific evaluation. On December 19, 2019, the FDA announced the licensing of the Ervebo (rVSVΔG-ZEBOV-GP) Ebola Vaccine. On February 15, 2020, Merck announced that African countries, including the Democratic Republic of the Congo, Burundi, Ghana, and Zambia, have approved the use of Ervebo. On January 8, 2021, the U.S. CDC's Advisory Committee on Immunization Practices (ACIP) recommended the use of the rVSVΔG-ZEBOV-GP Ebola vaccine (Ervebo) in the U.S. for preexposure vaccination for adults aged ≥18 years who are at the highest risk for potential occupational exposure to Ebola virus species Zaire ebolavirus because they are responding to an outbreak of EVD, work as health care personnel at federally designated Ebola treatment centers in the USA, or work as laboratorians or other staff at biosafety level 4 facilities in the USA.
Ervebo News
October 6, 2022 - Out of an abundance of caution, the U.S. CDC and the Department of Homeland Security Customs and Border Protection are applying new layers of screening at these five U.S. airports in response to the Sudan Ebolavirus outbreak in Uganda.
September 27, 2022 - The DRC ended a Zaire Ebola outbreak that recently reemerged in North Kivu Province. Over 500 people were vaccinated, including 350 contacts, contacts of contacts, and frontline workers.
September 20, 2022 - The WHO confirmed Uganda declared a Sudan Ebolavirus Disease outbreak.
August 17, 2022 - An analysis published by Virilogical found that of 131 contacts listed, 59 of the 60 HCWs are vaccinated in the DRC.
July 31, 2022 - To contribute to the humanitarian response to the 14th EVD outbreak in the Equateur province of the DRC, a DREF allocation was initially granted for four months, with an end date of August 31, 2022. This operation's new end date is September 30, 2022, for an overall implementation time of five months.
July 17, 2022 - The WHO Africa confirmed a Marburg Virus Disease outbreak in Ghana.
July 4, 2022 - The WHO confirmed that the just-ended outbreak in the DRC saw 2,104 people vaccinated, including 302 contacts and 1,307 frontline workers. To facilitate the vaccination rollout, an ultra-cold chain freezer was installed in Mbandaka, allowing vaccine doses to be stored locally, safely, and delivered effectively.
May 25, 2022 - The WHO Africa Tweeted: that 1,311 people in the DRC have been vaccinated in the Mbandaka & Wangata health zones in the DRC. The extremely high case-fatality ratio in this outbreak warrants concerted efforts.
May 10, 2022 - The UK's FCDO advises against all but essential travel to the province of Equateur in the DRC due to the ongoing outbreak of Zaire Ebola.
May 5, 2022 - The WHO African Region reported that 353 people were vaccinated in Mbandaka, the DRC.
April 27, 2022 - The DRC launched an Ebola vaccination in Mbandaka to halt the spread of the virus following an outbreak that has claimed two lives since 21 April. Around 200 doses of the rVSV-ZEBOV Ebola vaccine will be deployed.
April 24, 2022 - The Africa Pathogen Genomics Initiative - Africa CDC confirmed the recent case in the DRC that was vaccinated against the Ebola virus in 2020 and is not known to be an EVD survivor.
April 23, 2022 - The WHO Africa Region confirmed the DRC has stockpiles of the rVSV-ZEBOV Ebola vaccine available in Goma and Kinshasa, which will be sent to Mbandaka and administered through the 'ring vaccination strategy.
February 9, 2022 - A study by Liu et al. reports frequent Ebola virus persistence in the brain ventricular system of primates that survived acute disease after monoclonal antibody-based treatment. Viral persistence was associated with lethal recrudescence of Ebola, including severe inflammation in the brain. These findings have implications for long-term follow-up efforts to reduce individual disease relapse/recrudescence of viral persistence in survivors of EBOV infection.
February 8, 2022 - A study published by PNAS examined the antibody response at 21 days and six months postvaccination after a single dose of rVSVΔG-ZEBOV-GP among EVD-exposed and potentially exposed populations in the DRC. At 21 d of follow-up, 87.2% had an antibody response. Additionally, 95.6% demonstrated antibody persistence at six mo of follow-up. These findings give crucial evidence that antibody response and persistence after Ebola vaccination are robust in outbreak settings in the DRC.
December 16, 2021 - The WGO reported the Ebola outbreak that erupted in the DRC's North Kivu Province in October – the second in 2021 – was today declared over. In total, 11 cases (eight confirmed, three probable), including six deaths, were reported. More than 1800 people were vaccinated. The outbreak marks the first time the recently-licensed ERVEBO vaccine against Ebola was used in the DRC.
November 20, 2021 - The ECDC reported since the last report, no new EVD cases nor deaths have been reported in North Kivu province in the eastern region of the DRC. This Health Area is about 50km from Butembo City, where the DRC¶s 12th EVD outbreak occurred in 2021, lasting for around three months until it was declared over on May 3, 2021. In total, eight confirmed and three probable EVD cases, including nine deaths (six among the confirmed cases), were reported by WHO since the start of the outbreak on October 8, 2021, with the last confirmed case reported on October 30, 2021.
November 8, 2021 - The WHO Africa reported the overall case fatality rate of the current Ebola outbreak in the DRC is 81.8% (9/11) and 75.0% (6/8) among confirmed cases. And 485 persons have been vaccinated against EVD from the inception of the vaccination activities.
November 3, 2021 - The U.S. CDC's vaccine advisory committee vote supported using vaccines as PrEP for certain healthcare personnel and/or lab support staff at facilities that handle Ebola virus specimens.
November 2, 2021 - Additional cases and deaths were confirmed by the WHO in the Ebola virus disease outbreak in the DRC, with two new health areas affected. As of 30 October 2021, the Beni Health Zone reported 198 new alerts, including nine deaths. An additional 445 alerts, including 21 deaths, were notified from seven other HZs. A total of 394 people (67 primary care providers, including nine high-risk contacts, nine contacts of contacts, and 49 probable contacts) have been vaccinated, including 182 contacts of contacts, 125 probable contacts, and 87 high-risk contacts.
October 19, 2021 - The ECDC reported three people died, all from a DRC community in the Beni health zone. Ten patients are hospitalized, including two confirmed and eight suspected cases, and 386 contacts have been established so far, 322 followed in the last 24 hours, and 140 people have been vaccinated. The index case, diagnosed on 8 October and deceased in a health facility, had three family members who died in September, but they were not investigated for Ebola. The detected Ebola strain is 96% similar to the 10th EVD outbreak in the Democratic Republic of the Congo (2018-2020).
October 13, 2021 - The WHO confirmed a vaccination program had launched in the DRC related to the new Ebola outbreak. About 1,000 doses of the rVSV-ZEBOV Ebola vaccine and other medical supplies were delivered from the capital city of Kinshasa to Goma city in North Kivu. In addition, around 200 doses were sent to Beni City near the Butsili health area, where the confirmed case was detected. In addition, vaccinators are using the "ring vaccination" approach, where contacts and contacts of contacts are vaccinated. And the DRC has more than 12,000 vaccine doses in Kinshasa that can be deployed if necessary.
October 11, 2021 - The CEO of GAVI Tweeted, ' About 1,000 doses of the rVSV-ZEBOV vaccine are still available in the country (DRC), so vaccination can start immediately to contain this outbreak. And 248,500 supported doses are available in the global stockpile ready to ship in case of need' @GaviSeth.
October 10, 2021 - The WHO confirmed the recent case was a 3-year-old male who developed physical weakness, loss of appetite, abdominal pain, breathing difficulty, dark stool, and blood in their vomit. And they died on October 6th. This case follows a cluster of three deaths (two children and their father) who were the boy's neighbors. These three patients died on 14, 19, and 29 September 2021 after developing symptoms consistent with Ebola; however, none were tested for the virus. No vaccination plan was announced for the 'close contacts.'
October 8, 2021 - A case of Ebola has been confirmed in the DRC. The report from the biomedical lab, the INRB, said the positive result came from a 2-year-old in a densely populated neighborhood of BeniDRC's epicenters of the 2018-20 Ebola outbreak. The DRC's health minister declined to confirm the information.
August 17, 2021 - The WHO Africa confirmed the vaccine deployment from Guinea used 2,000 doses from Merck that are being used under the "ring strategy," where people who have come into contact with a confirmed Ebola patient are given the vaccine as first responders and health workers.
August 17, 2021 - The EMA published updated Procedural steps taken and scientific information after the Ervebo authorization.
April 1, 2021 - During the 2018–2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)–specific monoclonal antibody (mAb114), and he recovered within 14 days. However, six months later, he presented with severe EVD-like illness and EBOV viremia and died. We initiated epidemiologic and genomic investigations that showed that the patient had relapsed acute EVD, leading to a transmission chain resulting in 91 cases across six health zones over four months.
March 25, 2021 - UNICEF confirmed 4,345 people had been vaccinated, including 1,801 frontline staff, since the Ebvaccination'son's official launch in Guinea on February 23, 2021.
January 27, 2021 - The journal Nature published a new study: Ebola virus antibody decay–stimulation in a high proportion of survivors. The most increased antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5–2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered to prevent EBOV viral recrudescence in recovering individuals and mitigate the potential risk of reseeding an outbreak.
November 2, 2020 - More than 703 new people received the rVSV-ZEBOV-GP vaccine for 40,065 people vaccinated in the DRC.
February 14, 2020 - Merck confirmed that four African countries, including the Democratic Republic of the Congo, have approved the ERVEBO vaccine. ERVEBO has now been registered in the following African countries – DRC, Burundi, Ghana, and Zambia. Approvals in additional countries in Africa are anticipated shortly, said Merck. As previously announced, Merck is working to initiate licensed doses and expects these doses to start becoming available in approximately the third quarter of 2020.
December 19, 2019 - The U.S. FDA announced the approval of Ervebo, the first FDA-approved vaccine for preventing Ebola virus disease caused by Zaire ebolavirus.
May 23, 2019 - The School of Public Health Ethics Committee of the University of Kinshasa approved the compassionate belt vaccination protocol amendment for the rVSV-ZEBOV vaccine to expand its targets to pregnant women after the first trimester and lactating women identified as contacts. It is maintained for minors that children can be vaccinated from 6 years. Between 26 November 2018 and 26 May 2019, 319 pregnant women and 603 lactating women registered as contacts could not be vaccinated.
July 25, 2016 - Merck announced two regulatory milestones for its investigational vaccine for Ebola Zaire, V920 (rVSV∆G-ZEBOV-GP, live attenuated): the U.S. Food and Drug Administration has granted the vaccine candidate Breakthrough Therapy Designation, and the European Medicines Agency has granted PRIME status.
December 23, 2015 - Merck announced the Emergency Use Assessment and Listing application for its investigational Ebola Zaire vaccine, V920 (rVSV∆G-ZEBOV-GP, live attenuated), accepted for review by the World Health Organization.
Ervebo Clinical Trials
Merck Announces FDA Approval for ERVEBO® (Ebola Zaire Vaccine, Live). Clinical trial information is available at Merck Vaccines.
