Ervebo® (rVSVΔG-ZEBOV-GP) Ebola Vaccine
Merck 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), whose surface protein has been replaced with that of Ebola virus disease (EBOV). In addition, Merck's Ebola vaccine was genetically engineered to express the main glycoprotein from the Zaire ebolavirus to provoke a neutralizing immune response. Since vaccines do not contain germs in disease-causing forms, they will not give you the disease they are designed to prevent, says the U.S. Food and Drug Administration (FDA). As of September 7, 2023, Ervebo is indicated for preventing disease caused by Zaire ebolavirus in individuals 12 months of age and older living in Europe. On August 3, 2023, the FDA approved (STN: 125690) an expanded indication for Ervebo for individuals 12 months and older.
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 but not against other Ebolavirus (Sudan) or Marburgvirus species. 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). Merck and the U.S. government initially partnered in December 2014 through a third party, BioProtection Systems. In 2017, utilizing Project BioShield Act authority, U.S. BARDA funded work with Merck to continue late-stage development activities and began collaborating to expand ERVEBO's indication to include pediatrics.
Ervebo was first authorized by the European Medicines Agency (EMA) for the European Union on November 11, 2021 - (EMEA/H/C/004554). On July 20, 2023, the EMA's Committee for Medicinal Products for Human Use recommended the expanded approval of Ervebo for active immunization of individuals one year or older. In addition, it was Listed by the World Health Organization (WHO). The U.S. Food and Drug Administration (FDA) issued STN: BL 125690/0 on December 19, 2019, and STN: BL 125690/55 on July 27, 2023.
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. 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 Ervebo is highly effective against the Zaire ebolavirus but does not provide cross-protection against the Sudan ebolavirus or Marburgvirus.
Since the Ervebo vaccination program began in central Africa in 2019, approximately 300,000 persons have been vaccinated with the Ervebo vaccine. During the 2018–2020 Zaire EVD outbreak in the eastern part of the Democratic Republic of the Congo, about 99% of healthcare workers were vaccinated. Drugbank's Accession Number: DB15595. ATC code: J07BX02. STN: 125690. Clinical Reviewer: Rebecca Reindel.
New Jersey-based Merck Sharp & Dohme LLC 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 Vaccine Efficacy
On February 7, 2024, the Lancet Infectious Disease published an analysis of all 2,279 patients with confirmed Ebola virus disease. rVSVΔG-ZEBOV-GP vaccination significantly lowered case fatality risk (vaccinated: 25% [106/423] vs not vaccinated: 56% [570/1015]; p<0·0001). A related commentary stated this study shows that VSV-EBOV's protection extends beyond infection.
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. Based on cluster-level data, vaccine efficacy in the follow-up study was calculated to be 100% (95% CI: 79.3%–100%).
Ervebo Vaccine Availability
As of 2024, the Ervebo vaccine is recommended by the U.S. CDC, the EMA, and the United Kingdom for most people at high risk for potential exposure to the Ebola Zaire virus. Ervebo is licensed in the U.S., U.K., European Union, Canada, Switzerland, Burundi, Central African Republic, the Democratic Republic of the Congo, Ghana, Guinea, Rwanda, Uganda and Zambia.
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. As of March 2023, over 500,000 doses of the licensed vaccine have been delivered to the stockpile, administered by the International Coordinating Group on Vaccine Provision. Licensed healthcare providers interested in initial doses of ERVEBO for patients who meet the eligibility criteria should email [email protected] with the subject line: Request for ERVEBO.
This Ebola vaccine's inactive ingredients include recombinant human serum albumin and tromethamine (Tris) buffer, which contains a trace amount of rice protein.
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 (G.P.) antibody and/or Ebola G.P. nucleic acid or antigens. However, GP-based testing may have limited diagnostic value during vaccine viremia, in the presence of vaccine-derived Ebola G.P., 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.'
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.
Ervebo Side Effects
On December 14, 2022, the NEJM published an Original Article that confirmed the ERVEDO vaccine's safety and effectiveness. Do not administer ERVEBO to individuals with a history of a severe allergic reaction (e.g., anaphylaxis) to any vaccine component, including rice protein. Among 18,616 participants vaccinated with at least one dose of ERVEBO in clinical trials, there were two reports of anaphylaxis. 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%).
The safety and effectiveness of ERVEBO have not been assessed in immunocompromised individuals. The effectiveness of ERVEBO in immunocompromised individuals may be diminished. The risk of vaccination with ERVEBO, a live virus vaccine, in immunocompromised individuals, should be weighed against the risk of disease due to Zaire ebolavirus.
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 the 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 global stockpile of the Ebola vaccine, which was 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.
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. 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.
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.
Thermostable Second-Generation Zaire Ebolavirus Vaccine
Hilleman Laboratories announced in November 2022 a collaboration with MSD to develop a thermostable second-generation Zaire ebolavirus vaccine candidate building on MSD’s approved ERVEBO®. In November 2023, SK Bioscience forged a development licensing agreement with Hilleman Laboratories for this second-generation Zaire Ebola virus vaccine candidate.
Ervebo Vaccine Price
This vaccine is not commercially available in the U.S. This UNICEF table shows the 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 Vaccine News
November 28, 2023 - 9News reported Denver Health Regional Emerging Special Pathogen Treatment Center staff became some of the first people to receive the Ervebo Ebola vaccine for preventative measures.
September 7, 2023 - "Ebola virus disease is severe and potentially life-threatening for children and adults. The European Commission's expanded approval of ERVEBO for children one year of age and older is an important milestone for the prevention of disease caused by Zaire ebolavirus," said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories.
August 3, 2023 - "Ebola virus is contagious and potentially deadly in children and adults. We're proud of the approval of ERVEBO for the prevention of disease caused by Zaire ebolavirus in children as young as 12 months old, which is another milestone in our continued commitment to help address the global health threat caused by Zaire ebolavirus," said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories.
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 five U.S. airports in response to the Sudan Ebolavirus outbreak in Uganda.
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 an ultra-cold chain freezer was installed in Mband to facilitate the vaccination rollout, allowing vaccine doses to be stored locally, safely, and delivered effectively.
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.
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 prove that antibody response and persistence after Ebola vaccination are robust in outbreak settings in the DRC.
November 3, 2021 - The U.S. CDC's vaccine advisory committee voted to support using vaccines as PrEP for certain healthcare personnel and/or lab support staff at facilities that handle Ebola virus specimens.
October 19, 2021 - The ECDC reported three people died, all from a DRC community in the Beni health zone.
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. 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.
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."
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.
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.