rVSV-ZEBOV vaccine

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| target = Ebola virus

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| tradename = Ervebo

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| synonyms = V920,{{Cite journal |display-authors=6 |vauthors=Monath TP, Fast PE, Modjarrad K, Clarke DK, Martin BK, Fusco J, Nichols R, Heppner DG, Simon JK, Dubey S, Troth SP, Wolf J, Singh V, Coller BA, Robertson JS |date=April 2019 |title=rVSVΔG-ZEBOV-GP (also designated V920) recombinant vesicular stomatitis virus pseudotyped with Ebola Zaire Glycoprotein: Standardized template with key considerations for a risk/benefit assessment |journal=Vaccine |volume=1 |pages=100009 |doi=10.1016/j.jvacx.2019.100009 |pmc=6668225 |pmid=31384731 |doi-access=free |title-link=doi}} rVSVΔG-ZEBOV-GP Ebola vaccine{{Cite web |date=February 26, 2020 |title=Ebola Vaccine: Information about Ervebo |url=https://www.cdc.gov/vhf/ebola/clinicians/vaccine/index.html |url-status=live |archive-url=https://web.archive.org/web/20210416045913/https://www.cdc.gov/vhf/ebola/clinicians/vaccine/index.html |archive-date=April 16, 2021 |access-date=April 16, 2021 |website=Centers for Disease Control and Prevention (CDC)}}

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Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV), also known as Ebola Zaire vaccine live and sold under the brand name Ervebo, is an Ebola vaccine for adults that prevents Ebola caused by the Zaire ebolavirus.{{Cite web |date=March 7, 2023 |title=Ervebo (zaire ebolavirus- strain kikwit-95 envelope glycoprotein injection, solution |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2b1db7a1-c3f2-42e5-8499-91724edbf65e |url-status=live |archive-url=https://web.archive.org/web/20230305064047/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2b1db7a1-c3f2-42e5-8499-91724edbf65e |archive-date=March 5, 2023 |access-date=August 2, 2023 |website=DailyMed}}{{Cite journal |display-authors=6 |vauthors=Trad MA, Naughton W, Yeung A, Mazlin L, O'sullivan M, Gilroy N, Fisher DA, Stuart RL |date=January 2017 |title=Ebola virus disease: An update on current prevention and management strategies |journal=Journal of Clinical Virology |volume=86 |pages=5–13 |doi=10.1016/j.jcv.2016.11.005 |pmid=27893999 |doi-access=free |hdl-access=free |title-link=doi |hdl=10144/618818}}{{Cite journal |vauthors=Pavot V |date=December 2016 |title=Ebola virus vaccines: Where do we stand? |journal=Clinical Immunology |volume=173 |pages=44–49 |doi=10.1016/j.clim.2016.10.016 |pmid=27910805}} When used in ring vaccination, rVSV-ZEBOV has shown a high level of protection. Around half the people given the vaccine have mild to moderate adverse effects that include headache, fatigue, and muscle pain.{{Cite journal |vauthors=Medaglini D, Siegrist CA |date=April 2017 |title=Immunomonitoring of human responses to the rVSV-ZEBOV Ebola vaccine |journal=Current Opinion in Virology |volume=23 |pages=88–94 |doi=10.1016/j.coviro.2017.03.008 |pmid=28460340 |doi-access=free |hdl-access=free |title-link=doi |hdl=11365/1135960}}

rVSV-ZEBOV is a recombinant, replication-competent viral vector vaccine.{{Cite journal |vauthors=Marzi A, Ebihara H, Callison J, Groseth A, Williams KJ, Geisbert TW, Feldmann H |date=November 2011 |title=Vesicular stomatitis virus-based Ebola vaccines with improved cross-protective efficacy |journal=The Journal of Infectious Diseases |volume=204 |issue=Suppl 3 |pages=S1066–S1074 |doi=10.1093/infdis/jir348 |pmc=3203393 |pmid=21987743}} It consists of rice-derived recombinant human serum albumin and live attenuated recombinant vesicular stomatitis virus (VSV), which has been genetically engineered to express the main glycoprotein from the Zaire ebolavirus so as to provoke a neutralizing immune response to the Ebola virus.{{Cite journal |display-authors=6 |vauthors=Choi MJ, Cossaboom CM, Whitesell AN, Dyal JW, Joyce A, Morgan RL, Campos-Outcalt D, Person M, Ervin E, Yu YC, Rollin PE, Harcourt BH, Atmar RL, Bell BP, Helfand R, Damon IK, Frey SE |date=January 2021 |title=Use of Ebola Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020 |journal=MMWR. Recommendations and Reports |volume=70 |issue=1 |pages=1–12 |doi=10.15585/mmwr.rr7001a1 |pmc=7802368 |pmid=33417593 |doi-access=free}} {{PD-notice}}

The vaccine was approved for medical use in the European Union and the United States in 2019.{{Cite web |date=December 19, 2019 |title=Ervebo |url=http://www.fda.gov/vaccines-blood-biologics/ervebo |url-status=dead |archive-url=https://web.archive.org/web/20200429042333/https://www.fda.gov/vaccines-blood-biologics/ervebo |archive-date=April 29, 2020 |access-date=March 28, 2020 |publisher=U.S. Food and Drug Administration (FDA) |id=STN: 125690}} It was created by scientists at the National Microbiology Laboratory in Winnipeg, Manitoba, Canada, which is part of the Public Health Agency of Canada (PHAC). PHAC licensed it to a small company, Newlink Genetics, which started developing the vaccine; Newlink in turn licensed it to Merck in 2014. It was used in the DR Congo in a 2018 outbreak in Équateur province,{{Cite news |date=May 26, 2018 |title=Fear and failure: How Ebola sparked a global health revolution |url=https://edition.cnn.com/2018/05/26/health/ebola-outbreaks-west-africa-congo-revolution-mckenzie-intl/index.html |url-status=live |archive-url=https://web.archive.org/web/20190826101345/https://edition.cnn.com/2018/05/26/health/ebola-outbreaks-west-africa-congo-revolution-mckenzie-intl/index.html |archive-date=August 26, 2019 |access-date=May 26, 2018 |publisher=CNN |vauthors=McKenzie D}} and has since been used extensively in the 2018–20 Kivu Ebola outbreak, with over 90,000 people vaccinated.

Medical use

Nearly 800 people were ring vaccinated on an emergency basis with VSV-EBOV when another Ebola outbreak occurred in Guinea in March 2016.{{Cite web |date=March 2016 |title=WHO coordinating vaccination of contacts to contain Ebola flare-up in Guinea |url=https://www.who.int/en/news-room/feature-stories/detail/who-coordinating-vaccination-of-contacts-to-contain-ebola-flare-up-in-guinea |url-status=live |archive-url=https://web.archive.org/web/20200511053044/https://www.who.int/en/news-room/feature-stories/detail/who-coordinating-vaccination-of-contacts-to-contain-ebola-flare-up-in-guinea |archive-date=May 11, 2020 |access-date=May 14, 2016 |website=World Health Organization (WHO)}} In 2017, in the face of a new outbreak of Ebola in the Democratic Republic of the Congo, the Ministry of Health approved the vaccine's emergency use,{{Cite news |date=May 29, 2017 |title=Congo approves use of Ebola vaccination to fight outbreak |url=https://www.reuters.com/article/us-health-ebola-congo-idUSKBN18P0WN |url-status=live |archive-url=https://web.archive.org/web/20180927122250/https://www.reuters.com/article/us-health-ebola-congo-idUSKBN18P0WN |archive-date=September 27, 2018 |access-date=May 29, 2017 |work=Reuters}}{{Cite journal |vauthors=Maxmen A |year=2017 |title=Ebola vaccine approved for use in ongoing outbreak |url=https://www.nature.com/news/ebola-vaccine-approved-for-use-in-ongoing-outbreak-1.22024 |url-status=live |journal=Nature |doi=10.1038/nature.2017.22024 |archive-url=https://web.archive.org/web/20200120190018/https://www.nature.com/news/ebola-vaccine-approved-for-use-in-ongoing-outbreak-1.22024 |archive-date=January 20, 2020 |access-date=June 28, 2017|url-access=subscription }} but it was not immediately deployed.{{Cite report |title=Ebola Virus Disease Democratic Republic of the Congo: External Situation Report 22 |date=June 2017 |publisher=World Health Organization (WHO) Regional Office for Africa |hdl-access=free |hdl=10665/255645 |vauthors=((World Health Organization)), ((Regional Office for Africa)), ((Health Emergencies Programme))}}

=Effectiveness=

In April 2019, following a large-scale ring-vaccination scheme in the DRC outbreak, the WHO published the preliminary results of its research, in association with the DRC's Institut National pour la Recherche Biomedicale, into the effectiveness of the ring vaccination program, stating that the rVSV-ZEBOV-GP vaccine had been 97.5% effective at stopping Ebola transmission, relative to no vaccination.{{Cite web |date=April 16, 2019 |title=As Ebola outbreak rages, vaccine is 97.5% effective, protecting over 90K people |url=https://arstechnica.com/science/2019/04/ebola-vaccine-is-97-5-effective-early-outbreak-data-suggests/ |url-status=live |archive-url=https://web.archive.org/web/20210219092305/https://arstechnica.com/science/2019/04/ebola-vaccine-is-97-5-effective-early-outbreak-data-suggests/ |archive-date=February 19, 2021 |access-date=April 17, 2019 |website=Ars Technica |vauthors=Mole B}}{{Cite report |url=https://reliefweb.int/report/democratic-republic-congo/preliminary-results-efficacy-rvsv-zebov-gp-ebola-vaccine-using-ring |title=Ebola Ring Vaccination Results April 12, 2019 |date=April 12, 2019 |access-date=April 17, 2019 |archive-url=https://web.archive.org/web/20221106221933/https://reliefweb.int/report/democratic-republic-congo/preliminary-results-efficacy-rvsv-zebov-gp-ebola-vaccine-using-ring |archive-date=November 6, 2022 |url-status=live |website=World Health Organization (WHO)}}

Side effects

Systemic side effects include headache, feverishness, fatigue, joint and muscle pain, nausea, arthritis, rash, and abnormal sweating.{{Cite journal |vauthors=Martínez-Romero C, García-Sastre A |date=November 2015 |title=Against the clock towards new Ebola virus therapies |journal=Virus Research |volume=209 |pages=4–10 |doi=10.1016/j.virusres.2015.05.025 |pmid=26057711}}{{Cite journal |vauthors=Shuchman M |date=May 2015 |title=Ebola vaccine trial in west Africa faces criticism |journal=Lancet |volume=385 |issue=9981 |pages=1933–1934 |doi=10.1016/S0140-6736(15)60938-2 |pmid=25979835 |s2cid=40400570}}

Injection-site side events include injection-site pain, swelling, and redness.

Biochemistry

rVSV-ZEBOV is a live, attenuated recombinant vesicular stomatitis virus (VSV) in which the gene for the native envelope glycoprotein ({{UniProt|P03522}}) is replaced with that from the Ebola virus ({{UniProt|P87666}}), Kikwit 1995 Zaire strain.{{Cite journal |vauthors=Choi WY, Hong KJ, Hong JE, Lee WJ |date=January 2015 |title=Progress of vaccine and drug development for Ebola preparedness |journal=Clinical and Experimental Vaccine Research |volume=4 |issue=1 |pages=11–16 |doi=10.7774/cevr.2015.4.1.11 |pmc=4313103 |pmid=25648233}}{{Cite journal |display-authors=6 |vauthors=Regules JA, Beigel JH, Paolino KM, Voell J, Castellano AR, Hu Z, Muñoz P, Moon JE, Ruck RC, Bennett JW, Twomey PS, Gutiérrez RL, Remich SA, Hack HR, Wisniewski ML, Josleyn MD, Kwilas SA, Van Deusen N, Mbaya OT, Zhou Y, Stanley DA, Jing W, Smith KS, Shi M, Ledgerwood JE, Graham BS, Sullivan NJ, Jagodzinski LL, Peel SA, Alimonti JB, Hooper JW, Silvera PM, Martin BK, Monath TP, Ramsey WJ, Link CJ, Lane HC, Michael NL, Davey RT, Thomas SJ |date=January 2017 |title=A Recombinant Vesicular Stomatitis Virus Ebola Vaccine |journal=The New England Journal of Medicine |volume=376 |issue=4 |pages=330–341 |doi=10.1056/NEJMoa1414216 |pmc=5408576 |pmid=25830322}} Manufacturing of the vaccine for the Phase I trial was done by IDT Biologika.Hôpitaux Universitaires de Genève [http://www.hug-ge.ch/ebola-vaccine-candidate/faqs-vsv-zebov-vaccine-against-ebola-virus#22 FAQs about the context of this clinical trial: Question 22] {{Webarchive|url=https://web.archive.org/web/20181116212822/https://www.hug-ge.ch/ebola-vaccine-candidate/faqs-vsv-zebov-vaccine-against-ebola-virus#22 |date=November 16, 2018 }}[https://www.thestar.com/news/canada/2014/11/25/the_strange_tale_of_canadas_ebola_vaccine_walkom.html The strange tale of Canada's ebola vaccine: Walkom. Commercial rights to a vaccine worth $50 million were sold to a U.S. middleman for $205,000.] {{Webarchive|url=https://web.archive.org/web/20141126140251/http://www.thestar.com/news/canada/2014/11/25/the_strange_tale_of_canadas_ebola_vaccine_walkom.html |date=November 26, 2014 }} By Thomas Walkom, The Star, November 25, 2014 Manufacturing of vaccine for the Phase III trial was done by Merck, using the Vero cell line, which Merck already used to make its RotaTeq vaccine against rotavirus.Carly Helfand for FierceVaccine. November 21, 2014 {{usurped|1=[https://web.archive.org/web/20200630155156/http://www.fiercevaccines.com/story/bloomberg-newlink-merck-ebola-vaccine-production-talks/2014-11-21 NewLink, Merck sign Ebola vaccine licensing pact]}}Zachary Brennan for BioPharma Reporter. November 25, 2014. [http://www.biopharma-reporter.com/Bio-Developments/Merck-to-manufacture-NewLink-Ebola-vaccine-in-house Merck to manufacture NewLink Ebola vaccine in-house] {{Webarchive|url=https://web.archive.org/web/20210829023650/https://www.biopharma-reporter.com/Article/2014/11/25/Merck-to-manufacture-NewLink-Ebola-vaccine-in-house |date=August 29, 2021 }}

History

File:2014 ebola virus epidemic in West Africa simplified.svg

Scientists working for the Public Health Agency of Canada (PHAC) created the vaccine, and PHAC applied for a patent in 2003.{{Cite news |date=October 23, 2014 |title=Ebola Vaccine, Ready for Test, Sat on the Shelf |url=https://www.nytimes.com/2014/10/24/health/without-lucrative-market-potential-ebola-vaccine-was-shelved-for-years.html |url-status=live |archive-url=https://web.archive.org/web/20200614223041/https://www.nytimes.com/2014/10/24/health/without-lucrative-market-potential-ebola-vaccine-was-shelved-for-years.html |archive-date=June 14, 2020 |access-date=December 21, 2019 |work=The New York Times |vauthors=Grady D}}[https://patents.google.com/patent/WO2004011488A2/en Published PCT Application WO2004011488: Recombinant vesicular stomatitis virus vaccines for viral hemorrhagic fevers], claiming priority to US provisional patent application serial number 60/398,552 filed on July 26, 2003. From 2005, to 2009, three animal trials on the virus were published, all of them funded by the Canadian and U.S. governments. In 2005, a single intramuscular injection of the EBOV or MARV vaccine was found to induce completely protective immune responses in nonhuman primates (crab-eating macaques) against corresponding infections with the otherwise typically lethal EBOV or MARV.{{Cite journal |vauthors=Baize S |date=July 2005 |title=A single shot against Ebola and Marburg virus |journal=Nature Medicine |volume=11 |issue=7 |pages=720–721 |doi=10.1038/nm0705-720 |pmid=16015361 |s2cid=34226536}}{{Cite journal |display-authors=6 |vauthors=Jones SM, Feldmann H, Ströher U, Geisbert JB, Fernando L, Grolla A, Klenk HD, Sullivan NJ, Volchkov VE, Fritz EA, Daddario KM, Hensley LE, Jahrling PB, Geisbert TW |date=July 2005 |title=Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses |journal=Nature Medicine |volume=11 |issue=7 |pages=786–790 |doi=10.1038/nm1258 |pmid=15937495 |s2cid=5450135 |doi-access=free}}

In 2010, PHAC licensed the intellectual property on the vaccine to a small U.S. company called Bioprotection Systems, which was a subsidiary of Newlink Genetics, for US $205,000 and "low single-digit percentage" royalties.{{Cite news |date=October 20, 2014 |title=Canada urged to cancel Ebola vaccine licence, transfer rights to bigger company |url=https://www.ctvnews.ca/health/canada-urged-to-cancel-ebola-vaccine-licence-transfer-rights-to-bigger-company-1.2062134 |url-status=live |archive-url=https://web.archive.org/web/20150929071541/http://www.ctvnews.ca/health/canada-urged-to-cancel-ebola-vaccine-licence-transfer-rights-to-bigger-company-1.2062134 |archive-date=September 29, 2015 |access-date=January 10, 2020 |work=CTVNews |vauthors=Branswell H}} Newlink had funding from the U.S. Defense Threat Reduction Agency to develop vaccines.{{Cite web |date=October 6, 2014 |title=Sole Redacted License Agreement for Recombinant Vesicular Stomatitis Virus Vaccines for Viral Hemorrhagic Fevers |url=http://www.phac-aspc.gc.ca/id-mi/vhf-fvh/licen-recombinant-vaccin-eng.php |url-status=live |archive-url=https://web.archive.org/web/20170722213510/http://www.phac-aspc.gc.ca/id-mi/vhf-fvh/licen-recombinant-vaccin-eng.php |archive-date=July 22, 2017 |access-date=August 4, 2015 |publisher=Public Health Agency of Canada}}

In December 2013, the largest-ever Ebola epidemic started in West Africa, specifically, in Guinea.{{Cite report |url=https://www.who.int/csr/disease/ebola/one-year-report/virus-origin/en/ |title=Origins of the 2014 Ebola epidemic |date=January 2015 |publisher=World Health Organization (WHO) |access-date=October 8, 2016 |archive-url=https://web.archive.org/web/20150120232805/http://www.who.int/csr/disease/ebola/one-year-report/virus-origin/en/ |archive-date=January 20, 2015 |url-status=dead}} On August 12, the WHO ruled that offering people infected with Ebola the RVSV-ZEBOV vaccine (which at the time was untested on humans) was ethical, and the Canadian government donated 500 doses of the vaccine to the WHO.{{Cite news |date=August 12, 2014 |title=Exclusive: Canada to donate its own Ebola vaccine to WHO for use in Africa |url=https://www.reuters.com/article/us-health-ebola-vaccine-canada-idUSKBN0GC1YU20140812 |url-status=live |archive-url=https://web.archive.org/web/20200630061842/https://www.reuters.com/article/us-health-ebola-vaccine-canada-idUSKBN0GC1YU20140812 |archive-date=June 30, 2020 |access-date=January 10, 2020 |work=Reuters}}{{Cite web |last=Public Health Agency of Canada |date=August 2, 2013 |title=Fact Sheet - VSV-EBOV - Canada's vaccine for Ebola |url=https://www.canada.ca/en/public-health/services/infectious-diseases/fact-sheet-ebov-canada-s-experimental-vaccine-ebola.html |url-status=live |archive-url=https://web.archive.org/web/20200422211934/https://www.canada.ca/en/public-health/services/infectious-diseases/fact-sheet-ebov-canada-s-experimental-vaccine-ebola.html |archive-date=April 22, 2020 |access-date=January 10, 2020}} In October 2014, Newlink had no vaccine in production and no human trials underway, and there were calls for the Canadian government to cancel the contract. In September or October 2014, Newlink formed a steering committee among the interested parties, including PHAC, the NIH, and the WHO, to plan the clinical development of the vaccine.Patricia Van Arnum for DCAT. October 21, 2014 [http://connect.dcat.org/blogs/patricia-van-arnum/2014/10/21/pharma-companies-seek-to-ramp-up-production-for-experimental-ebola-treatments Pharmaceutical companies join the effort to develop and produce vaccines and treatments for the Ebola virus] {{Webarchive|url=https://web.archive.org/web/20160204153319/http://connect.dcat.org/blogs/patricia-van-arnum/2014/10/21/pharma-companies-seek-to-ramp-up-production-for-experimental-ebola-treatments |date=February 4, 2016 }}{{Cite web |date=October 8, 2014 |title=Canadian Ebola vaccine safety trials move ahead, NewLink Genetics says |url=http://www.cbc.ca/news/health/canadian-ebola-vaccine-safety-trials-move-ahead-newlink-genetics-says-1.2792722 |url-status=live |archive-url=https://web.archive.org/web/20161204063816/http://www.cbc.ca/news/health/canadian-ebola-vaccine-safety-trials-move-ahead-newlink-genetics-says-1.2792722 |archive-date=December 4, 2016 |access-date=October 21, 2014 |publisher=CBC News |vauthors=Branswell H}}

In October 2014, Newlink Genetics began a Phase I clinical trial of rVSV-ZEBOV on healthy human subjects to evaluate the immune response, identify any side effects and determine the appropriate dosage.{{Cite news |date=October 13, 2014 |title=Ebola outbreak: 1st human trials of Canadian vaccine start in U.S. |url=http://www.cbc.ca/news/world/ebola-outbreak-1st-human-trials-of-canadian-vaccine-start-in-u-s-1.2796859 |url-status=live |archive-url=https://web.archive.org/web/20191120113324/https://www.cbc.ca/news/world/ebola-outbreak-1st-human-trials-of-canadian-vaccine-start-in-u-s-1.2796859 |archive-date=November 20, 2019 |access-date=October 13, 2014 |publisher=CBC News |agency=Associated Press}}{{Cite news |date=October 8, 2014 |title=Canadian Ebola vaccine license holder moving ahead with safety trials |url=http://o.canada.com/health/canadian-ebola-vaccine-license-holder-moving-ahead-with-safety-trials |url-status=dead |archive-url=https://web.archive.org/web/20141012002046/http://o.canada.com/health/canadian-ebola-vaccine-license-holder-moving-ahead-with-safety-trials |archive-date=October 12, 2014 |access-date=October 13, 2014 |publisher=Canadian Press |vauthors=Branswell H}}{{Cite web |date=October 9, 2014 |title=A Phase 1 Randomized, Double-Blind, Placebo Controlled, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of Prime-Boost VSV Ebola Vaccine in Healthy Adults |url=http://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2015-I-0001.html |url-status=dead |archive-url=https://web.archive.org/web/20141017091751/http://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2015-I-0001.html |archive-date=October 17, 2014 |access-date=October 13, 2014 |publisher=National Institute of Allergy and Infectious Diseases (NIAID)}} Phase I trials took place in Gabon, Kenya, Germany, Switzerland, the US, and Canada.Hôpitaux Universitaires de Genève [http://www.hug-ge.ch/ebola-vaccine-candidate/faqs-about-context-clinical-trial#10 FAQs about the context of this clinical trial: Question 10] {{Webarchive|url=https://web.archive.org/web/20191030232450/https://www.hug-ge.ch/ebola-vaccine-candidate/faqs-about-context-clinical-trial#10 |date=October 30, 2019 }}{{Cite report |url=https://www.who.int/medicines/ebola-treatment/ebola_vaccine_clinicaltrials/en/ |title=Table of vaccine clinical trials |access-date=October 14, 2016 |archive-url=https://web.archive.org/web/20151022074907/http://www.who.int/medicines/ebola-treatment/ebola_vaccine_clinicaltrials/en/ |archive-date=October 22, 2015 |url-status=dead |website=World Health Organization (WHO)}} In November 2014, Newlink exclusively licensed rights to the vaccine to Merck{{Cite news |date=November 24, 2014 |title=Merck & Co. Licenses NewLink's Ebola Vaccine Candidate |url=http://www.genengnews.com/gen-news-highlights/merck-co-licenses-newlink-s-ebola-vaccine-candidate/81250631 |url-status=dead |archive-url=https://web.archive.org/web/20180518055647/https://www.genengnews.com/gen-news-highlights/merck-co-licenses-newlink-s-ebola-vaccine-candidate/81250631 |archive-date=May 18, 2018 |access-date=January 20, 2016 |work=Genetic Engineering & Biotechnology News}} for US $50 million plus royalties.{{Cite news |date=November 24, 2014 |title=Canadian Ebola vaccine development taken over by Merck |url=https://www.cbc.ca/news/health/canadian-ebola-vaccine-development-taken-over-by-merck-1.2847128 |url-status=live |archive-url=https://web.archive.org/web/20180402075111/http://www.cbc.ca/news/health/canadian-ebola-vaccine-development-taken-over-by-merck-1.2847128 |archive-date=April 2, 2018 |access-date=January 10, 2020 |agency=Reuters}}

The Phase I study started with a high dose which caused arthritis and skin reactions in some people, and the vaccine was found replicating in the synovial fluid of the joints of the affected people; the clinical trial was halted because of that, then recommenced with a lower dose.{{Cite journal |vauthors=Medaglini D, Harandi AM, Ottenhoff TH, Siegrist CA |date=December 2015 |title=Ebola vaccine R&D: Filling the knowledge gaps |journal=Science Translational Medicine |volume=7 |issue=317 |pages=317ps24 |doi=10.1126/scitranslmed.aad3106 |pmc=6858855 |pmid=26659569 |doi-access=free |title-link=doi}}

In March 2015, a Phase II clinical trial and a Phase III started in Guinea at the same time; the Phase II trial focused on frontline health workers, while the Phase III trial was a ring vaccination in which close contacts of people who had contracted Ebola virus were vaccinated with VSV-EBOV.{{Cite web |date=July 17, 2015 |title=Q&A on trial of Ebola Virus Disease vaccine in Guinea |url=https://www.who.int/medicines/ebola-treatment/q_a_vaccine_trial_guinea/en/ |url-status=dead |archive-url=https://web.archive.org/web/20191115050920/https://www.who.int/medicines/ebola-treatment/q_a_vaccine_trial_guinea/en/ |archive-date=November 15, 2019 |access-date=November 14, 2019 |website=World Health Organization (WHO)}}{{Cite web |date=July 31, 2015 |title=Ebola vaccine is 'potential game-changer' |url=https://www.bbc.co.uk/news/health-33733711 |url-status=live |archive-url=https://web.archive.org/web/20191230202918/https://www.bbc.co.uk/news/health-33733711 |archive-date=December 30, 2019 |access-date=July 30, 2015 |website=BBC News Online |vauthors=Gallagher J |location=UK}}

In January 2016, the GAVI Alliance signed an agreement with Merck under which Merck agreed to provide VSV-EBOV vaccine for future outbreaks of Ebola and GAVI paid Merck {{US$|5 million}}; Merck will use the funds to complete clinical trials and obtain regulatory approval. As of that date, Merck had submitted an application to the World Health Organization (WHO) through their Emergency Use Assessment and Listing (EUAL) program to allow for use of the vaccine in the case of another epidemic.{{Cite news |date=January 20, 2016 |title=Vaccines alliance signs $5 million advance deal for Merck's Ebola shot |url=https://www.reuters.com/article/us-health-ebola-vaccine-idUSKCN0UY0OT |url-status=live |archive-url=https://web.archive.org/web/20190705120823/https://www.reuters.com/article/us-health-ebola-vaccine-idUSKCN0UY0OT |archive-date=July 5, 2019 |access-date=January 20, 2016 |work=Reuters |vauthors=Hirshler B, Kelland K}} It was used on an emergency basis in Guinea in March 2016.

Results of the Phase III Guinea trial were published in December 2016. It was widely reported in the media that vaccine was safe and appeared to be nearly 100% effective,{{Cite book |title=Integrating Clinical Research Into Epidemic Response: The Ebola Experience |vauthors=Keusch G, McAdam K, Cuff P, Mancher M, Busta ER |collaboration=Health Committee on Clinical Trials During the 2014-2015 Ebola Outbreak, Board on Health Sciences Policy, Division of Health And Medicine, National Academies of Sciences, Engineering, and Medicine |publisher=National Academies Press (US) |year=2017 |isbn=978-0-309-45776-7 |veditors=Keusch G, McAdam K, Cuff P, Mancher M, Busta ER |location=Washington (DC) |doi=10.17226/24739 |pmid=28696651}}{{Cite journal |vauthors=Geisbert TW |date=February 2017 |title=First Ebola virus vaccine to protect human beings? |journal=Lancet |volume=389 |issue=10068 |pages=479–480 |doi=10.1016/S0140-6736(16)32618-6 |pmid=28017402 |doi-access=free |title-link=doi}} but the vaccine remained unavailable for commercial use as of December 2016.{{Cite web |date=December 27, 2016 |title=Ebola vaccine highly effective in final trial results |url=http://www.cidrap.umn.edu/news-perspective/2016/12/ebola-vaccine-highly-effective-final-trial-results |url-status=live |archive-url=https://web.archive.org/web/20200417152727/https://www.cidrap.umn.edu/news-perspective/2016/12/ebola-vaccine-highly-effective-final-trial-results |archive-date=April 17, 2020 |access-date=December 28, 2016 |website=CIDRAP |vauthors=Schnirring L}}

In April 2017, scientists from the U.S. National Academy of Medicine (NAM) published a review of the response to the Ebola outbreak that included a discussion of how clinical trial candidates were selected, how trials were designed and conducted, and reviewed the data resulting from the trials. The committee found that data from the Phase III Guinea trial were difficult to interpret for several reasons. The trial had no placebo arm; it was omitted for ethical reasons and everyone involved, including the committee, agreed with the decision. This left only a delayed treatment group to serve as a control, but this group was eliminated after an interim analysis showed high levels of protection, which left the trial even more underpowered. The committee found that under an intention-to-treat analysis, the rVSV-ZEBOV vaccine might have had no efficacy, agreed with the authors of the December 2016 report that it probably had some efficacy, but found statements that it had substantial or 100% efficacy to be unsupportable.

In April 2019, following a large-scale ring-vaccination scheme in the DRC outbreak, preliminary results showed that the vaccine had been 97.5% effective at stopping Ebola transmission, relative to no vaccination.

In September 2019, the US Food and Drug Administration (FDA) accepted Merck's Biologics License Application and granted priority review for the vaccine.{{Cite press release |title=FDA Accepts Merck's Biologics License Application (BLA) and Grants Priority Review for V920, the Company's Investigational Vaccine for Ebola Zaire Virus |date=September 17, 2019 |url=https://www.businesswire.com/news/home/20190917005341/en/FDA-Accepts-Merck%E2%80%99s-Biologics-License-Application-BLA |via=Business Wire |access-date=September 17, 2019}}

In October 2019, the European Medicines Agency (EMA) recommended granting conditional marketing authorization for the rVSV-ZEBOV-GP vaccine.{{Cite press release |title=Major milestone for WHO-supported Ebola vaccine |date=October 18, 2019 |url=https://www.who.int/news-room/detail/18-10-2019-major-milestone-for-who-supported-ebola-vaccine |access-date=October 19, 2019 |url-status=live |archive-url=https://web.archive.org/web/20191111221609/https://www.who.int/news-room/detail/18-10-2019-major-milestone-for-who-supported-ebola-vaccine |archive-date=November 11, 2019 |website=World Health Organization (WHO)}}{{Cite press release |title=First vaccine to protect against Ebola |date=October 18, 2019 |url=https://www.ema.europa.eu/en/news/first-vaccine-protect-against-ebola |access-date=November 11, 2019 |url-status=live |archive-url=https://web.archive.org/web/20191111220233/https://www.ema.europa.eu/en/news/first-vaccine-protect-against-ebola |archive-date=November 11, 2019 |website=European Medicines Agency (EMA)}}{{Cite web |date=October 17, 2019 |title=Ervebo |url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/ervebo |url-status=live |archive-url=https://web.archive.org/web/20191115054131/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/ervebo |archive-date=November 15, 2019 |access-date=November 15, 2019 |website=European Medicines Agency (EMA)}}

In November 2019, the European Commission granted a conditional marketing authorization to Ervebo{{Cite web |date=October 16, 2019 |title=Ervebo EPAR |url=https://www.ema.europa.eu/en/medicines/human/EPAR/ervebo |url-status=live |archive-url=https://web.archive.org/web/20210308035916/https://www.ema.europa.eu/en/medicines/human/EPAR/ervebo |archive-date=March 8, 2021 |access-date=March 29, 2020 |website=European Medicines Agency (EMA)}}{{Cite press release |title=Merck's Ervebo [Ebola Zaire Vaccine (rVSVΔG-ZEBOV-GP) live] Granted Conditional Approval in the European Union |date=November 11, 2019 |publisher=Merck |url=https://www.businesswire.com/news/home/20191111005601/en/Merck%E2%80%99s-ERVEBO%C2%AE-Ebola-Zaire-Vaccine-rVSV%CE%94G-ZEBOV-GP-live |via=Business Wire |access-date=November 11, 2019 |url-status=live |archive-url=https://web.archive.org/web/20191111221058/https://www.businesswire.com/news/home/20191111005601/en/Merck%E2%80%99s-ERVEBO%C2%AE-Ebola-Zaire-Vaccine-rVSV%CE%94G-ZEBOV-GP-live |archive-date=November 11, 2019}} and the World Health Organization (WHO) prequalified an Ebola vaccine for the first time, indicating that the vaccine met WHO standards for quality, safety and efficacy, and allowing UN agencies and GAVI to procure vaccine for distributions.{{Cite press release |title=WHO prequalifies Ebola vaccine, paving the way for its use in high-risk countries |date=November 12, 2019 |url=https://www.who.int/news-room/detail/12-11-2019-who-prequalifies-ebola-vaccine-paving-the-way-for-its-use-in-high-risk-countries |access-date=November 13, 2019 |url-status=live |archive-url=https://web.archive.org/web/20191115045218/https://www.who.int/news-room/detail/12-11-2019-who-prequalifies-ebola-vaccine-paving-the-way-for-its-use-in-high-risk-countries |archive-date=November 15, 2019 |website=World Health Organization (WHO)}}

In December 2019, Ervebo was approved for use in the United States.{{Cite press release |title=First FDA-approved vaccine for the prevention of Ebola virus disease, marking a critical milestone in public health preparedness and response |date=December 19, 2019 |publisher=U.S. Food and Drug Administration (FDA) |url=https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-ebola-virus-disease-marking-critical-milestone-public-health |access-date=December 19, 2019 |url-status=dead |archive-url=https://web.archive.org/web/20191220052152/https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-ebola-virus-disease-marking-critical-milestone-public-health |archive-date=December 20, 2019}} {{PD-notice}}

The approval of Ervebo was supported by a study conducted in Guinea during the 2014-2016 outbreak in individuals 18 years of age and older. The study was a randomized cluster (ring) vaccination study in which 3,537 contacts, and contacts of contacts, of individuals with laboratory-confirmed Ebola virus disease (EVD) received either "immediate" or 21-day "delayed" vaccination with Ervebo. This noteworthy design was intended to capture a social network of individuals and locations that might include dwellings or workplaces where a patient spent time while symptomatic, or the households of individuals who had contact with the patient during that person's illness or death. In a comparison of cases of EVD among 2,108 individuals in the "immediate" vaccination arm and 1,429 individuals in the "delayed" vaccination arm, Ervebo was determined to be 100% effective in preventing Ebola cases with symptom onset greater than ten days after vaccination. No cases of EVD with symptom onset greater than ten days after vaccination were observed in the "immediate" cluster group, compared with ten cases of EVD in the 21-day "delayed" cluster group.

In additional studies, antibody responses to Ervebo were assessed in 477 individuals in Liberia, approximately 500 individuals in Sierra Leone and approximately 900 individuals in Canada, Spain, and the US. The antibody responses among those in the study conducted in Canada, Spain and the US were similar to those among individuals in the studies conducted in Liberia and Sierra Leone.

The safety of Ervebo was assessed in approximately 15,000 individuals in Africa, Europe and North America. The most commonly reported side effects were pain, swelling and redness at the injection site, as well as headache, fever, joint and muscle aches and fatigue.

The application for Ervebo in the United States was granted priority review, a tropical disease priority review voucher, and breakthrough therapy designation. The US Food and Drug Administration (FDA) granted approval for Ervebo to Merck & Co., Inc.

Merck discontinued development of the related rVSV vaccines for Marburg virus (rVSV-MARV) and Sudan ebolavirus (rVSV-SUDV). Merck returned the rights on these vaccines back to Public Health Agency of Canada. The knowledge on developing rVSV vaccines which Merck gained with GAVI funding remains Merck's, and cannot be used by anyone else wishing to develop a rVSV vaccine.{{Cite web |date=September 25, 2018 |title=MSF's response to CEPI's policy regarding equitable access |url=https://msfaccess.org/msfs-response-cepis-policy-regarding-equitable-access |url-status=live |archive-url=https://web.archive.org/web/20210321163753/https://msfaccess.org/msfs-response-cepis-policy-regarding-equitable-access |archive-date=March 21, 2021 |access-date=April 10, 2020 |website=Médecins Sans Frontières Access Campaign |language=en |quote=In vaccine development, access to know how is important. Knowledge and expertise including but not limited to purification techniques, cell lines, materials, software codes and their transfer of this to alternative manufacturers in the event the awardee discontinues development of a promising vaccine is critically important. The recent example of Merck abandoning the development of rVSV vaccines for Marburg (rVSV-MARV) and for Sudan-Ebola (rVSV-SUDV) is a case in point. Merck continues to retain vital know-how on the rVSV platform as it developed the rVSV vaccine for Zaire-Ebola (rVSV-ZEBOV) with funding support from GAVI. While it has transferred the rights on these vaccines back to Public Health Agency of Canada, there is no mechanism to share know how on the rVSV platform with other vaccine developers who would like to also use rVSV as a vector against other pathogens.}}

In July 2023, the FDA expanded the approval of Ervebo for use in people aged 12 months through 17 years of age. Ervebo was approved for use in people aged 18 years of age and older in December 2019.{{Cite press release |title=FDA Roundup: July 28, 2023 |date=July 28, 2023 |publisher=U.S. Food and Drug Administration (FDA) |url=https://www.fda.gov/news-events/press-announcements/fda-roundup-july-28-2023 |access-date=August 2, 2023}} {{PD-notice}}

Ebola 2018

Image:Ebola Geimpfte Kongo.png: Number of rVSV-ZEBOV vaccinated persons in the epidemic area DRC{{Cite web |title=Ebola RDC – Evolution de la riposte contre l'épidémie d'Ebola dans les provinces du Nord Kivu et de l'Ituri au Lundi 31 décembre 2018 |url=https://mailchi.mp/sante.gouv.cd/ebola_kivu_31dec |url-status=live |archive-url=https://web.archive.org/web/20200624213218/https://mailchi.mp/sante.gouv.cd/ebola_kivu_31dec |archive-date=June 24, 2020 |access-date=December 31, 2018 |website=us13.campaign-archive.com}}]]

=2018 Democratic Republic of the Congo Ebola virus outbreak=

During an outbreak in the Democratic Republic of the Congo in 2018, the ZEBOV vaccine was used,{{Cite news |title=Congo to begin vaccinating against Ebola |url=https://www.cnn.com/2018/05/21/africa/ebola-vaccine-outbreak-drc-intl/index.html |url-status=live |archive-url=https://web.archive.org/web/20181125084525/https://www.cnn.com/2018/05/21/africa/ebola-vaccine-outbreak-drc-intl/index.html |archive-date=November 25, 2018 |access-date=July 2, 2018 |work=CNN |vauthors=Berlinger J}} and what was once contact tracing which numbered 1,706 individuals (ring vaccination which totaled 3,330) was reduced to zero on June 28, 2018.{{Cite web |title=Ebola RDC – Communication spéciale du Ministre de la Santé concernant l'évolution de la neuvième épidémie d'Ebola en RDC |url=https://us13.campaign-archive.com/?u=89e5755d2cca4840b1af93176&id=2cf40db8ea |url-status=live |archive-url=https://web.archive.org/web/20200422022732/https://us13.campaign-archive.com/?u=89e5755d2cca4840b1af93176&id=2cf40db8ea |archive-date=April 22, 2020 |access-date=July 2, 2018 |website=us13.campaign-archive.com}} The outbreak completed the required 42-day cycle on July 24.{{Cite journal |year=2018 |title=Weekly Bulletin on Outbreak and other Emergencies: Week 26: 23–29 June 2018 |journal=Weekly Bulletin on Outbreaks and Other Emergencies: 1–23 |publisher=World Health Organization, Regional Office for Africa |hdl-access=free |hdl=10665/272981}}{{Cite web |date=June 29, 2018 |title=WHO AFRO Outbreaks and Other Emergencies, Week 26: 23 - 29 June 2018 (Data as reported by 17:00; 29 June 2018) - World |url=https://reliefweb.int/report/world/who-afro-outbreaks-and-other-emergencies-week-26-23-29-june-2018-data-reported-1700-29 |url-status=live |archive-url=https://web.archive.org/web/20210414180934/https://reliefweb.int/report/world/who-afro-outbreaks-and-other-emergencies-week-26-23-29-june-2018-data-reported-1700-29 |archive-date=April 14, 2021 |access-date=January 30, 2022 |website=ReliefWeb}}{{Cite web |date=July 17, 2018 |title=Congo Ebola Outbreak Expected to End Next Week |url=https://www.voanews.com/a/congo-ebola-outbreak-expected-to-end-next-week/4486095.html |url-status=live |archive-url=https://web.archive.org/web/20180717164317/https://www.voanews.com/a/congo-ebola-outbreak-expected-to-end-next-week/4486095.html |archive-date=July 17, 2018 |access-date=July 17, 2018 |website=VOA |vauthors=Schlein L}}{{Cite web |date=July 23, 2018 |title=Media Advisory: Expected end of Ebola outbreak |url=https://reliefweb.int/report/democratic-republic-congo/media-advisory-expected-end-ebola-outbreak |url-status=live |archive-url=https://web.archive.org/web/20180723164918/https://reliefweb.int/report/democratic-republic-congo/media-advisory-expected-end-ebola-outbreak |archive-date=July 23, 2018 |access-date=July 23, 2018 |website=ReliefWeb}}{{Cite press release |title=Ebola outbreak in DRC ends: WHO calls for international efforts to stop other deadly outbreaks in the country |url=https://www.who.int/news-room/detail/24-07-2018-ebola-outbreak-in-drc-ends--who-calls-for-international-efforts-to-stop-other-deadly-outbreaks-in-the-country |access-date=July 24, 2018 |website=World Health Organization (WHO)}}

=2018 Kivu Ebola outbreak=

On August 1, 2018, an EVD outbreak was declared in North Kivu DRC. After six months the current totals stand at 735 total cases and 371 deaths; violence in the region has helped the spread of the virus.{{Cite web |title=Ebola RDC – Evolution de la riposte contre l'épidémie d'Ebola dans les provinces du Nord Kivu et de l'Ituri au Vendredi 4 janvier 2019 |url=https://mailchi.mp/sante.gouv.cd/ebola_kivu_4jan19 |url-status=live |archive-url=https://web.archive.org/web/20191111222504/https://mailchi.mp/sante.gouv.cd/ebola_kivu_4jan19 |archive-date=November 11, 2019 |access-date=January 5, 2019 |website=us13.campaign-archive.com |language=fr}}{{Cite web |title=Statement on disruptions to the Ebola response in the Democratic Republic of the Congo |url=https://www.who.int/news-room/detail/28-12-2018-statement-on-disruptions-to-the-ebola-response-in-the-democratic-republic-of-the-congo |url-status=live |archive-url=https://web.archive.org/web/20181229211307/https://www.who.int/news-room/detail/28-12-2018-statement-on-disruptions-to-the-ebola-response-in-the-democratic-republic-of-the-congo |archive-date=December 29, 2018 |access-date=January 5, 2019 |website=World Health Organization (WHO)}}{{Cite news |date=August 1, 2018 |title=Congo declares new Ebola outbreak in eastern province |url=https://www.reuters.com/article/us-health-ebola/congo-declares-new-ebola-outbreak-in-eastern-province-idUSKBN1KM59B?il=0 |url-status=live |archive-url=https://web.archive.org/web/20200624212647/https://www.reuters.com/article/us-health-ebola/congo-declares-new-ebola-outbreak-in-eastern-province-idUSKBN1KM59B?il=0 |archive-date=June 24, 2020 |access-date=January 5, 2019 |work=Reuters |vauthors=Mahamba F}}

Preliminary results show ring vaccination with the vaccine has been highly effective at reducing Ebola transmission.