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. 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.
rVSV-ZEBOV is a recombinant, replication-competent viral vector vaccine. 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.
The vaccine was approved for medical use in the European Union and the United States in 2019. 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, and has since been used extensively in the 2018–20 Kivu Ebola outbreak, with over 90,000 people vaccinated.
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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. 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.
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.
Side effects
Systemic side effects include headache, feverishness, fatigue, joint and muscle pain, nausea, arthritis, rash, and abnormal sweating.
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 (P03522) is replaced with that from the Ebola virus (P87666), 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 the Vero cell line, 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, 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 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 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.
Ebola 2018
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 June 28, 2018. The outbreak completed the required 42-day cycle on July 24.
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.
Preliminary results show ring vaccination with the vaccine has been highly effective at reducing Ebola transmission.