rVSV-ZEBOV vaccine
electron micrograph of the Ebola virus | |
Vaccine description | |
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Target | Ebola virus |
Vaccine type | Recombinant vector |
Clinical data | |
Trade names | Ervebo |
Other names | V920,[1] rVSVΔG-ZEBOV-GP Ebola vaccine[2] |
AHFS/Drugs.com | Monograph |
License data | |
Intramuscular | |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
CAS Number | |
DrugBank | |
ChemSpider |
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UNII |
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
rVSV-ZEBOV is a
The vaccine was approved for medical use in the European Union and the United States in 2019.
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.[19] 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,[20][21] but it was not immediately deployed.[22]
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
Side effects
Systemic side effects include headache, feverishness, fatigue, joint and muscle pain, nausea, arthritis, rash, and abnormal sweating.[8][23][24][4] Injection-site side events include injection-site pain, swelling, and redness.[4]
Biochemistry
rVSV-ZEBOV is a live, attenuated
History
Scientists working for the Public Health Agency of Canada (PHAC) created the vaccine, and PHAC applied for a patent in 2003.[15][16][31] From 2005, to 2009, three animal trials on the virus were published, all of them funded by the Canadian and U.S. governments.[28] 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.[32][16]
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.[33] Newlink had funding from the U.S. Defense Threat Reduction Agency to develop vaccines.[15][34][35]
In December 2013, the
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.[34][41][42] Phase I trials took place in Gabon, Kenya, Germany, Switzerland, the US, and Canada.[43][44] In November 2014, Newlink exclusively licensed rights to the vaccine to Merck[17] for US $50 million plus royalties.[45]
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.[46]
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.[47][48]
In January 2016, the
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,[50][51] but the vaccine remained unavailable for commercial use as of December 2016.[52]
In April 2017, scientists from the U.S.
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.[9][10]
In September 2019, the US
In October 2019, the European Medicines Agency (EMA) recommended granting conditional marketing authorization for the rVSV-ZEBOV-GP vaccine.[54][55][56]
In November 2019, the European Commission granted a conditional marketing authorization to Ervebo[5][57] 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.[58]
In December 2019, Ervebo was approved for use in the United States.[13]
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.[13] 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.[13] 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.[13] 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.[13] 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.[13]
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.[13] 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.[13]
The safety of Ervebo was assessed in approximately 15,000 individuals in Africa, Europe and North America.[13] 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.[13]
The application for Ervebo in the United States was granted priority review, a tropical disease priority review voucher, and breakthrough therapy designation.[13] The US Food and Drug Administration (FDA) granted approval for Ervebo to Merck & Co., Inc.[13]
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.[59]
In July 2023, the FDA expanded the approval of Ervebo for use in people aged 12 months through 17 years of age.[60] Ervebo was approved for use in people aged 18 years of age and older in December 2019.[60]
Ebola 2018
2018 Democratic Republic of the Congo Ebola virus outbreak
During an
2018 Kivu Ebola outbreak
On August 1, 2018, an
Preliminary results show ring vaccination with the vaccine has been highly effective at reducing Ebola transmission.[9][10]
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- ^ Carly Helfand for FierceVaccine. November 21, 2014 NewLink, Merck sign Ebola vaccine licensing pact Archived June 30, 2020, at the Wayback Machine
- ^ Zachary Brennan for BioPharma Reporter. November 25, 2014. Merck to manufacture NewLink Ebola vaccine in-house Archived August 29, 2021, at the Wayback Machine
- ^ Published PCT Application WO2004011488: Recombinant vesicular stomatitis virus vaccines for viral hemorrhagic fevers Archived October 20, 2016, at the Wayback Machine, claiming priority to US provisional patent application serial number 60/398,552 filed on July 26, 2003.
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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.
- ^ a b "FDA Roundup: July 28, 2023" (Press release). U.S. Food and Drug Administration (FDA). July 28, 2023. Retrieved August 2, 2023. This article incorporates text from this source, which is in the public domain.
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Further reading
- "Scientists hail '100% effective' Ebola vaccine". National Health Service. England. August 3, 2015. Archived from the original on November 15, 2019. Retrieved November 15, 2019.
- Marzi A, Robertson SJ, Haddock E, Feldmann F, Hanley PW, Scott DP, et al. (August 2015). "EBOLA VACCINE. VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain". Science. 349 (6249): 739–742. PMID 26249231.
External links
- Ebola Vaccines at the U.S. National Library of Medicine Medical Subject Headings (MeSH)