Target disease Ebola virus ChemSpider none | Type Recombinant vector | |
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Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV) is an experimental vaccine for protection against Ebola virus disease. Results of a clinical trial published in December 2016 found the vaccine to be 70–100% effective in preventing infection and to have mild to moderate side effects. How long the benefits last is unclear.
Contents
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, 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 unavailable for commercial use as of December 2016.
Medical use
rVSV-ZEBOV is a candidate vaccine against Ebola virus disease. Results of a clinical trial were published in December 2016; the study found the vaccine to be 70–100% effective in preventing infection.
Onset of effectiveness is believed to occur within five days. How long the benefits last is unclear.
Side effects
Side effects are generally mild to moderate. They may include joint pain, feeling tired, headache, pain at the site of injection, and muscle pains.
Chemistry
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.
History
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. Nearly 800 people were ring vaccinated with VSV-EBOV when another Ebola outbreak occurred in Guinea in March 2016.