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 Ebola vaccines are vaccines either approved or in development to prevent Ebola. As of 2022, there are only vaccines against the Zaire ebolavirus. The first vaccine to be approved in the United States was rVSV-ZEBOV in December 2019. It had been ...

for adults that prevents

Ebola Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after becom ...

caused by the

Zaire ebolavirus ''Zaire ebolavirus'', more commonly known as Ebola virus (; EBOV), is one of six known species within the genus '' Ebolavirus''. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and o ...

. When used in

ring vaccination Ring vaccination is a strategy to inhibit the spread of a disease by vaccinating those who are most likely to be infected. This strategy vaccinates the contacts of confirmed patients, and people who are in close contact with those contacts. Thi ...

, 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 A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material ( DNA), which can be transcribed by the recipient's host cells as mRNA coding for a desired protein (or: antigen) to elicit an immune response. , six viral v ...

. It consists of rice-derived recombinant human serum albumin and live attenuated recombinant

vesicular stomatitis virus ''Indiana vesiculovirus'', formerly ''Vesicular stomatitis Indiana virus'' (VSIV or VSV) is a virus in the family ''Rhabdoviridae''; the well-known ''Rabies lyssavirus'' belongs to the same family. VSIV can infect insects, cattle, horses and pigs ...

(VSV), which has been genetically engineered to express the main

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

from the

so as to provoke a neutralizing

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

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 The National Microbiology Laboratory (NML) is part of the Public Health Agency of Canada (PHAC), the agency of the Government of Canada that is responsible for public health, health emergency preparedness and response, and infectious and chronic d ...

Winnipeg, Manitoba Winnipeg () is the capital and largest city of the province of Manitoba in Canada. It is centred on the confluence of the Red and Assiniboine rivers, near the longitudinal centre of North America. , Winnipeg had a city population of 749,6 ...

, Canada, which is part of the

Public Health Agency of Canada The Public Health Agency of Canada (PHAC; french: Agence de la santé publique du Canada, ASPC) is an agency of the Government of Canada that is responsible for public health, emergency preparedness and response, and infectious and chronic diseas ...

(PHAC). PHAC licensed it to a small company, Newlink Genetics, which started developing the vaccine; Newlink in turn licensed it to

Merck Merck refers primarily to the German Merck family and three companies founded by the family, including: * the Merck Group, a German chemical, pharmaceutical and life sciences company founded in 1668 ** Merck Serono (known as EMD Serono in the Unite ...

in 2014. It was used in the

DR Congo The Democratic Republic of the Congo (french: République démocratique du Congo (RDC), colloquially "La RDC" ), informally Congo-Kinshasa, DR Congo, the DRC, the DROC, or the Congo, and formerly and also colloquially Zaire, is a country in ...

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.

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 The Institut National de la Recherche Biomédicale (INRB) is the national medical research organization of the Democratic Republic of the Congo. The responsible ministry is the Ministry of Scientific Research and Technology. The National Biomedic ...

, into the effectiveness of the ring vaccination program, stating that the

rVSV-ZEBOV-GP 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 ...

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

(VSV) in which the gene for the native envelope

() is replaced with that from the

Ebola virus ''Zaire ebolavirus'', more commonly known as Ebola virus (; EBOV), is one of six known species within the genus ''Ebolavirus''. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and ot ...

(),

Kikwit Kikwit is the largest city of Kwilu Province, lying on the Kwilu River in the southwestern part of the Democratic Republic of the Congo. Kikwit is also known in the region under the nickname "The Mother". The population is approximately 458,000 ( ...

1995 Zaire strain. Manufacturing of the vaccine for the Phase I trial was done by IDT Biologika.The strange tale of Canada's ebola vaccine: Walkom. Commercial rights to a vaccine worth $50 million were sold to a U.S. middleman for $205,000.
By Thomas Walkom, The Star, November 25, 2014 Manufacturing of vaccine for the Phase III trial was done by

, using the Vero cell line, which Merck already used to make its

RotaTeq Rotavirus vaccine is a vaccine used to protect against rotavirus infections, which are the leading cause of severe diarrhea among young children. The vaccines prevent 15–34% of severe diarrhea in the developing world and 37–96% of s ...

vaccine against

rotavirus ''Rotavirus'' is a genus of double-stranded RNA viruses in the family ''Reoviridae''. Rotaviruses are the most common cause of diarrhoeal disease among infants and young children. Nearly every child in the world is infected with a rotavirus a ...

History

2014 ebola virus epidemic in West Africa simplified

Scientists working for the

(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 macaque The crab-eating macaque (''Macaca fascicularis''), also known as the long-tailed macaque and referred to as the cynomolgus monkey in laboratories, is a cercopithecine primate native to Southeast Asia. A species of macaque, the crab-eating macaqu ...

s) 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 The Defense Threat Reduction Agency (DTRA) is a combat support agency within the United States Department of Defense (DoD) for countering weapons of mass destruction (WMD; chemical, biological, radiological, nuclear, and high explosives). Accor ...

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

for US $50 million plus royalties. The Phase I study started with a high dose which caused

arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...

and skin reactions in some people, and the vaccine was found replicating in the

synovial fluid Synovial fluid, also called synovia, elp 1/sup> is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its egg white–like consistency, the principal role of synovial fluid is to reduce friction between the articular ...

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

in which close contacts of people who had contracted Ebola virus were vaccinated with VSV-EBOV. In January 2016, the

GAVI Alliance GAVI, officially Gavi, the Vaccine Alliance (previously the GAVI Alliance, and before that the Global Alliance for Vaccines and Immunization) is a Public–private partnership, public–private global health partnership with the goal of incr ...

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 The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...

(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. 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 The National Academy of Medicine (NAM), formerly called the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, En ...

(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 In medicine an intention-to-treat (ITT) analysis of the results of a randomized controlled trial is based on the initial treatment assignment and not on the treatment eventually received. ITT analysis is intended to avoid various misleading artifac ...

, 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 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. In September 2019, the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) accepted Merck's

Biologics License Application A biologics license application (BLA) is defined by the U.S. Food and Drug Administration (FDA) as follows: The biologics license application is a request for permission to introduce, or deliver for introduction, a biologic product into inters ...

and granted

priority review Priority review is a program of the United States Food and Drug Administration (FDA) to expedite the review process for drugs that are expected to have a particularly great impact on the treatment of a disease. The priority review voucher program ...

for the vaccine. In October 2019, the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(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

(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 GAVI, officially Gavi, the Vaccine Alliance (previously the GAVI Alliance, and before that the Global Alliance for Vaccines and Immunization) is a public–private global health partnership with the goal of increasing access to immunization ...

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. 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. 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. 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. 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. 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 U.S. The antibody responses among those in the study conducted in Canada, Spain and the U.S. were similar to those among individuals in the studies conducted in Liberia and Sierra Leone. The safety of Ervebo was assessed in approximately 15,000 individuals in Africa, Europe and North America. 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. The application for Ervebo in the United States was granted

, a tropical disease priority review voucher, and

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "br ...

designation. The U.S.

(FDA) granted approval for Ervebo to Merck & Co., Inc. Merck discontinued development of the related rVSV vaccines for

Marburg virus Marburg virus (MARV) is a hemorrhagic fever virus of the ''Filoviridae'' family of viruses and a member of the species '' Marburg marburgvirus'', genus ''Marburgvirus''. It causes Marburg virus disease in primates, a form of viral hemorrhagic f ...

( 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

funding remains Merck's, and cannot be used by anyone else wishing to develop a rVSV vaccine.

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.

References

External links

* * {{DEFAULTSORT:Rvsv-Zebov Vaccine Breakthrough therapy Ebola Health in West Africa Merck & Co. brands Viral vector vaccines West African Ebola virus epidemic Orphan drugs