Ervebo® (rVSVΔG-ZEBOV-GP) Ebola Vaccine Clinical Trials, Dosage, Efficacy, Indication, Side Effects
Merck Ervebo® Ebola Vaccine (rVSV-ZEBOV-GP, rVSV-ZEBOV, v920) is a live, recombinant, replication-competent Orthoebolavirus zairense 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, the Ervebo vaccine was genetically engineered to express the main glycoprotein from the Zaire ebolavirus to provoke a neutralizing immune response. In November 2019, the World Health Organization (WHO) prequalified Ervebo. 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. On August 3, 2023, the FDA approved (STN: 125690) an expanded indication for Ervebo for individuals 12 months and older. In Canada, Ervebo was approved in November 2022.
Ervebo was granted Conditional Approval by the European Medicines Agency (EMA) for the European Union on November 11, 2019 - (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. As of September 7, 2023, Ervebo is indicated by the EMA (EMA/344888/2023) to prevent disease caused by Zaire ebolavirus in individuals 12 months of age and older living in Europe.
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.
As of April 25, 2024, the U.S. CDC reported most doses (139,120; 95%) shipped from the ICG stockpile since 2021 have been repurposed for preventive vaccination of high-risk groups, compared with 6,570 (5%) used for outbreak response. The WHO Annexes to the recommendations for the use of the Ebola vaccines Evidence to the decision was published in June 2024. 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
The Lancet Infectious Diseases published real-world study results on August 20, 2024, that found that rVSV-ZEBOV was 84% effective against infection and supported its use during outbreaks, even in challenging contexts such as in the eastern Democratic Republic of the Congo. On May 9, 2024, a preprint study published by The Lancet concluded that new data add further evidence of rVSV-ZEBOV safety and immunogenicity, including in people with pre-existing antibodies from suspected natural ZEBOV infection, which do not blunt the rVSV-ZEBOV immune response. Pre-vaccination serological screening is not required.
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 Booster Dose
The Lancet Microbe published results from a study on October 4, 2024, that concluded in marked contrast to earlier trials evaluating short-term boosting, delaying a rVSVΔG-ZEBOV-GP booster until month 18 resulted in an increase in GMT that remained several-fold above the no-booster group GMT for at least 18 months. These findings could have implications for defining the optimal timing of booster doses as pre-exposure prophylaxis in populations at ongoing risk for Ebola virus exposure.
Ervebo Vaccine Availability
As of October 2024, the Ervebo vaccine 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. To date, more than 130,000 doses of ERVEBO® have been shipped from the stockpile for vaccination campaigns in the Democratic Republic of the Congo, Guinea-Bissau, and Uganda, in addition to 7,000 vaccines shipped for outbreak response vaccination.
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 currently with antiviral medication, the vaccine's effectiveness, immune globulin, and/or blood or plasma transfusions are unknown. The WHO published the revised Ebola Vaccine FAQ, and the U.S. CDC published Ebola Vaccine: Information for U.S. Healthcare Providers. Merck says, Do not administer Ervebo to individuals with a severe allergic reaction (e.g., anaphylaxis) to any vaccine component, including rice protein.
Ervebo Dosage
The Ervebo vaccine is administered as a single-dose intramuscular injection, which is given at the top of your arm.
Ervebo Booster Dose
The U.S. FDA approves initial doses of ERVEBO for the prevention of EVD. Since an Ervebo vaccine booster dose is not an EMA or FDA-approved indication, the U.S. CDC sponsored an expanded access Investigational New Drug program in April 2022, allowing booster dose administration for pre-exposure prophylaxis in adults who were previously vaccinated at least six months before vaccination, and who have potential risk of occupational exposure to EBOV.
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 and swellvaccine'sredness.
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, and its effectiveness 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.
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).
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 Immvaccine 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 fedCDC'sy 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. Additional Ebola vaccine price information is available at InstantRx™.
Ervebo Vaccine News
November 28, 2023 - 9News reported the Denver Health Regional Emerging Special Pathogen Treatment Center staff received the Ervebo vaccine for preventative measures.
September 7, 2023 - "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 R" search Laboratories.
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 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 13, 2021 - The WHO confirmed a vaccination program had launched in the DRC related to the new Ebola outbreak.
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 stock and pile and ready to ship in case of. need' @GaviSeth.
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 approved the ERVEBO vaccine. ERVEBO has now been registered in the following African countries – DRC, Burundi, Ghana, and Zambia.
December 19, 20—The U.S. FDA announced the approval of Ervebo, the first FDA-approved vaccine for preventing the Ebola virus disease caused by the 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.
