An electron micrograph of the Ebola virus
|Target disease||Ebola virus|
Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV) is an experimental vaccine for protection against Ebola virus disease. As of April 2017, ring vaccination with rVSV-ZEBOV appeared to be somewhat effective, but the extent of efficacy was uncertain. When used in ring-vaccination, rVSV-EBOV 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.
rVSV-ZEBOV is a recombinant, replication-competent vaccine. It consists of a vesicular stomatitis virus (VSV), which has been genetically engineered to express a glycoprotein from the Zaire ebolavirus so as to provoke a neutralizing immune response to the Ebola virus.
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 is being used in DR Congo in a 2018 outbreak.
As of April 2017[update], ring vaccination with rVSV-EBOV appeared to be somewhat effective, but the extent of efficacy was uncertain, due to the trial design and elimination of the delayed treatment arm part way through the trial.
Nearly 800 people were ring vaccinated on an emergency basis with VSV-EBOV when another Ebola outbreak occurred in Guinea in March 2016. 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,, but it was not immediately deployed.
rVSV-ZEBOV is a live, attenuated recombinant vesicular stomatitis virus in which the gene for the native envelope glycoprotein is replaced with that from the Ebola virus, Kikwit 1995 Zaire strain. Manufacturing of the vaccine for the Phase I trial was done by IDT Biologika. Manufacturing of vaccine for the Phase III trial was done by Merck, using cells from African green monkeys, which Merck already used to make its RotaTeq vaccine against rotavirus.
Scientists working for the Public Health Agency of Canada (PHAC) created the vaccine, and PHAC applied for a patent in 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.
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; Newlink had funding from the U.S. Defense Threat Reduction Agency to develop vaccines.
In December 2013, the largest-ever Ebola epidemic started in West Africa, specifically, in Guinea. 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.
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. Phase I trials took place in Gabon, Kenya, Germany, Switzerland, the US, and Canada. In November 2014 NewLink exclusively licensed rights to the vaccine to Merck.
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.
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. Preliminary results were reported in July. In the same report, the WHO communicated that the control arm of the trial was dropped and the trial would expand.
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 through their Emergency Use Assessment and Listing (EUAL) program to allow for use of the vaccine in the case of another epidemic. 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, but the vaccine remained unavailable for commercial use as of December 2016.
In April 2017, scientists from the U.S. National Academy of Medicine 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.
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, and what was once contact tracing which numbered 1,706 individuals (ring vaccination which totaled 3,330) was reduced to zero on 28 June 2018. The outbreak will complete the required 42-day cycle on 24 July.
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|Wikinews has related news: Study confirms efficacy of NewLink Genetics ebola vaccine|
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