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 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. 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. 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. 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 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 for US $50 million plus royalties. 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. 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 ; 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. It was used on an emergency basis in Guinea in March 2016. but the vaccine remained unavailable for commercial use as of December 2016. 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 October 2019, the
European Medicines Agency (EMA) recommended granting
conditional marketing authorization for the rVSV-ZEBOV-GP vaccine. In November 2019, the European Commission granted a conditional marketing authorization to Ervebo 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. In December 2019, Ervebo was approved for use in the United States. 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. In July 2023, the FDA expanded the approval of Ervebo for use in people aged 12 months through 17 years of age. ==Ebola 2018==