A timeline of selected events related to VSV-EBOV
file=7042 lores-Ebola-Zaire-CDC Photo.jpg VSV-EBOV or rVSV-filovirus-GP type of vaccine, is an experimental vaccine for the Ebola filovirus, ' viral hemorrhagic fever (VHF), developed by a team of scientists at the National Microbiology Laboratory [1] [2] of the Public Health Agency of Canada (PHAC) in c.2003 . The vaccine contains a gene for the Ebola surface protein stitched into a livestock pathogen known as vesicular stomatitis virus (VSV). [3] According to Dr. Gregory Taylor of the PHAC, "This vaccine, the product of many years of scientific research and innovation, could be an important tool in curbing the outbreak." VSV-EBOV vaccine was found to be 100% effective in protecting Nonhuman primates (NHP) from Ebola and is now being rushed through human trials - "after sitting unused on a lab shelf for ten years. The VSV-EBOV vaccine had its results "published in a respected journal," [4] and "health officials called them exciting." [5] [6]
VSV-EBOV uses an Ebola virus protein spliced into a weakened strain of a different virus, vesicular stomatitis virus (VSV), [7] which typically afflicts cattle. The weakened viral strain is modified to express an Ebola virus protein to help trigger an immune response to Ebola." [8]
It costs a few million dollars for academic researchers to "develop a prototype drug or vaccine that works in animals." But "tests in humans and scaling up production can cost hundreds of millions, and bringing a new vaccine all the way to market typically costs $1 billion to $1.5 billion." [9]
"While vaccines normally are preventatives, the VSV-EBOV vaccine has shown effectiveness in studies on animals after they were exposed to the virus. It may be used soon after someone was exposed to infection, similar to the way rabies shots are used now, said Gary Kobinger, chief of special pathogens for the Public Health Agency of Canada." [10]
By 2014 there were several experimental ebola vaccines considered by WHO but the VSV-EBOV is considered to be the most promising as it requires only one injection.
The U.S. National Institutes of Health is planning a larger, human study in early 2015 to test another experimental Ebola vaccine co-developed by the NIH and GlaxoSmithKline PLC GSK, -0.03%. [8]
Johnson & Johnson JNJ, -0.17% also is developing an experimental vaccine in partnership with Bavarian Nordic of Denmark. [8]
The family Filoviridae include Ebola virus and Marburg virus. The Ebola virus was first identified in 1976. [5] Since then "no previous Ebola outbreak has been as large or persistent as the current epidemic." [5] The most widespread epidemic of Ebola virus disease in history which emerged again in 2013 is ongoing in 2014 in several West African countries. [11] [12] [13] According to the World Health Organization, by October 2014, the Ebola outbreak in West Africa had already killed more than 4,500 people. [14]
The Public Health Agency of Canada holds the patent associated with the rVSV-filovirus-GP type of vaccine.
From 1999 to 2008, Dr. Feldmann held the position of chief of the special pathogens program of the National Microbiology Laboratory, Public Health Agency of Canada. [15] At a conference in Germany in 2000 Dr. Thomas Geisbert of University of Texas Medical Branch and Dr. Heinz Feldman of the highest level containment required to safely work with deadly viruses, Biosafety level four (BSL-4) [16] at the National Microbiology Laboratory in Winnipeg, decided to work together to develop an Ebola vaccine. [17] They tested the vaccine on monkeys with a 100% success rate and published their findings in 2005 and 2011. [4] The "Galveston National Laboratory at the University of Texas Medical Branch also has a Biosafety level four (BSL-4) facility. [16]
"The development of the vaccines started in 2001 at the National Microbiology Laboratory (NML) in Winnipeg, in partnership with the then-Faculty of Medicine at the University of Manitoba (it’s now the College of Medicine in the Faculty of Health Sciences). At the time, Jones was professor of immunology and Feldmann, a professor of medical microbiology. The research was supported by a Canadian Institutes of Health Research grant through the U of M. Following initial trials, work was carried out in partnership with the U.S. Army Medical Research Institute of Infectious Diseases in what was being considered a landmark in international scientific collaboration."
[18] The VSV-EBOV "vaccine went into non-human primate (monkey) trials in late 2003. The monkeys were 100 percent protected."
[17] In 2003 scientists from the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland and the United States Army Medical Research Institute of Infectious Diseases reported on the results of an experimental vaccine which successfully protected non-human primates (cynomolgus macaques) against ebola. At that Thomas W. Geisbert was associated with the United States Army Medical Research Institute of Infectious Diseases in Maryland
[19] and he co-authored a paper entitled Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates with eight fellow scientists at the
Vaccine Research Center,
National Institute of Allergy and Infectious Diseases,
National Institutes of Health,
Bethesda, Maryland and the
United States Army Medical Research Institute of Infectious Diseases,
Fort Detrick, Maryland.
In 2005 Steven M Jones, Heinz Feldmann, Ute Ströher, Joan B Geisbert, Lisa Fernando, Allen Grolla, Hans-Dieter Klenk, Nancy J Sullivan, Viktor E Volchkov, Elizabeth A Fritz, Kathleen M Daddario, Lisa E Hensley, Peter B Jahrling & Thomas W Geisbert published the results of their very successful vaccine trials on monkeys in the journal Nature Medicine. A single injection of the "EBOV or MARV vaccine elicited completely protective immune responses in nonhuman primates against lethal EBOV or MARV challenges." [20] [17] In 2005 Dr. Kobinger moved back to Canada in 2005 bringing his Ebola research with him. [21] The Public Health Agency of Canada provided start-up funds and provided space for Kobinger's team. [21] Financial support came the Canadian Department of National Defence's Chemical, Biological, Radiological and Nuclear Research and Technology Initiative.
The central role in ebola research played by National Microbiology Laboratory in Winnipeg is credited to Heinz Feldmann, the lab's first special pathogens chief and Gary Kobinger, his successor and the current branch chief. [22] The National Microbiology Laboratory produced "ZMapp, the most promising of the current experimental treatments", an Ebola vaccine that may be useful both to prevent infection and stop it in its tracks" and "a mobile diagnostic lab that has changed the way outbreak testing is done." [22]
Dr. Frank Plummer was director of NML from 2000 to March 2014 when he stepped down for health reasons. Plummer has been battling health problems over the past year; he finished his final term in the job at the end of March. [23] According to Canadian Press journalist Branswell, scientific and public health leaders were "very concerned about the way the government is going about filling the job and the job posting itself." [23] There was only a "[t]he three-week window to apply, the lack of attention drawn to the opening, and the salary scale offered — starting at $132,600 — suggested to a number of people that the federal government might be seeking a bureaucrat, not a top-notch scientist, to replace Plummer, who is a world-renowned HIV researcher." [24]
"The posting did not stipulate that candidates must be experienced scientists, nor did it ask that they have published scientific papers. It calls for experience managing the delivery of health-related programs, providing strategic scientific advice and representing an organization nationally and internationally. The wording of the posting even suggests someone could be named to the job without having either a medical degree or a PhD."
— Branswell 2014d
The National Microbiology Laboratory in Winnipeg and the "Galveston National Laboratory at the University of Texas Medical Branch [are facilities] with the highest level containment required to safely work with deadly viruses, Biosafety level four (BSL-4)." [16]
From 1999 to 2008, Dr. Feldmann held the position of chief of the special pathogens program of the National Microbiology Laboratory, Public Health Agency of Canada. [25]
In 2005 Dr. Kobinger moved back to Canada in 2005 bringing his Ebola research with him. [21] The Public Health Agency of Canada provided start-up funds and provided space for Kobinger's team. [21] Financial support came the Canadian Department of National Defence's Chemical, Biological, Radiological and Nuclear Research and Technology Initiative.
"The vaccine was produced in Winnipeg by the Public Health Agency of Canada, and is the product of more than 10 years of scientific research by Public Health Agency of Canada scientists at the National Microbiology Laboratory. The Canadian government patented it, and 800 to 1,000 vials of the vaccine were produced. [6]
By September 2007 Dr. Gary Kobinger was working at the mobile field laboratory that the National Public Health Agency of Canada had in Mweka, Congo. [26]
By 2012 funding for the Kobinger's research was a concern. Their major financial source, the Defence Research and Development Canada, was "hit hard by cuts in March 2012 federal budget; microbiology research is not high on its agenda." [21] Marc Fortin, CEO of Defence Research and Development Canada, said that "areas of highest priority" for the organization are cyber security and the Arctic. "Other areas now require less DRDC support." [21]
"The Canadian research was done under the leadership of Dr. Gary Kobinger who heads the special pathogens research program at the national laboratory. His team had developed a cocktail of three monoclonal antibodies called ZMApp, the rights to which were recently acquired by LeafBio of San Diego, Calif." [26] In the 1990s as a youth in Montreal during the AIDS epidemic Kobinger watched documentaries that became catalysts for his career which led him from medical school in Montreal to research in Philadelphia. In Philadelphia he focused on the Ebola virus. [21] "Ebola binds strongly to these cells, so Gary Kobinger at the University of Pennsylvania in Philadelphia tried adding a surface protein from Ebola to HIV. Initial tests on mice showed the hybrid virus was very efficient: the gene it carried was active in 24 per cent of airway cells after two months, a far better proportion than achieved by other delivery methods. [27] ZMapp is a hybrid of two earlier monoclonal cocktails, one made by Kobinger’s team and the other by scientists at the U.S. Army Medical Research Institute of Infectious Diseases in Frederick, Md. [28] Gary Kobinger is the "chief of special pathogens at Winnipeg’s National Microbiology Laboratory and the scientist who led the development of the vaccine." [29] According to a Globe and Mail article published August 2014, [29]
"Dr. Kobinger and his colleagues at the Winnipeg lab also developed two of the three mono-clonol antibodies that form the basis of an experimental Ebola treatment known as ZMapp, which received widespread scrutiny after limited doses were offered to two U.S. health-care workers and a Spanish priest, but not to Africans...
In July 2014 Dr. Kobinger and his team were involved in ebola-related work in Sierra Leone. When he returned to Canada he told the Canadian Press that the use of the experimental drugs would be too risky. [29]
"These are all experimental drugs that have not met the requirements … even for a Phase 1 [trial] right now in humans. So they have to pass all the toxicity [tests], they have to pass the safety trials.
— Dr. Kobinger July 2014
In an interview with the Boston Globe, Thomas W. Geisbert, a a virologist and "Ebola expert at the University of Texas, Galveston and one of the developers of the vaccine, made a statement," [9] [6]
"'There's never been a big market for Ebola vaccines... So big pharma, who are they going to sell it to?... It takes a crisis sometimes to get people talking. 'OK. We've got to do something here.'" [9] [6]
At a conference in Germany in 2000 Dr. Thomas Geisbert of University of Texas Medical Branch and Dr. Heinz Feldman of the Level 4 Containment Laboratory at the National Microbiology Laboratory in Winnipeg, decided to work together to develop an Ebola vaccine. [17] They tested the vaccine on monkeys with a 100% success rate and published their findings in 2005 and 2011. [4] Nonhuman primate (NHP)
John Eldridge, chief scientific officer for Profectus BioSciences Inc., based in Baltimore.
"University of Ottawa professor Amir Attaran published a letter in the British medical journal ''The Lancet'' calling for Canada to withdraw from its agreement with NewLink." [30] [31]
Attaran is calling on the Ottawa to change the licensing agreement, which now says that Canada should get a commercial return on the vaccine, to make sure commercial considerations play no role in the fight against Ebola.
In an interview on 20 November 2014, Professor Attaran argued that the existing licensing agreement between NewLink and the Government of Canada needed to be changed to ensure that commercial considerations are not part of the decisions made to combat ebola. He said, [31]
"The arrangements have to ensure that very poor people, the poorest in the world, get this vaccine without paying a price they can’t afford.... So far, the Government of Canada has demanded a maximum commercial return. That will have to change for that to succeed."
— Professor Attaran 20 November 2014
Iowa-based NewLink Genetics acquired the commercial license to develop rVSV-ZEBOV in 2010 for use in humans, in its wholly owned subsidiary BioProtection Systems at the Iowa State University Research Park in Ames, Iowa. [32]
BioProtections Systems, an emerging biotechnology company, is a wholly-owned subsidiary of GenLinks Corporation, located in the ISU Research Park in Ames, Iowa. [33]
"BioProtection Systems Corporation (BPSC) is an emerging biotechnology company located in the Iowa State University Research Park in Ames, Iowa. The company is developing innovative vaccine solutions to increase the United States’ biodefense capabilities. BioProtection Systems Corporation is collaborating with NewLink Genetics’ experienced biomedical and bioinformatics professionals to exploit new vaccine technologies."
— ISU Research Park 2014
Iowa-based NewLink Genetics has the license to develop rVSV-ZEBOV for use in humans, in its wholly owned subsidiary BioProtection Systems at the Iowa State University Research Park in Ames, Iowa. [32] In this work, BioProtection Systems is supported by the U.S. Defense Threat Reduction Agency, of the United States Department of Defense. [34] The role of Newlink Genetics appears to be mainly the organization of clinical trials in the U.S., as it has no production facilities for the vaccine. [26] Canada had roughly 1,500 vials of vaccine made for clinical trials before the 2014 Ebola outbreak began in West Africa. The license with Newlink has come under criticism. Amir Attaran, a professor of law and population health at the University of Ottawa, has urged that the license be cancelled because of the limitations of such a small company with little experience in this area. [35] The license was awarded when there seemed to be no urgency for an Ebola vaccine, and hence little interest from large pharmaceutical companies.
Between 1994 and the present, there have been many Ebola virus outbreaks, caused by 4 different strains of the virus, affecting mostly people living in central Africa, and the health care providers trying to treat them. Ebola viruses are members of the filoviridae virus family, which also includes the dangerous Marburg virus. It causes severe and often deadly infection called a viral hemorrhagic fever, characterized by organ failure, bleeding, and death.
— NewLinks Genetics 2014
"Canada surrenders its commercial self-interest to the Company; and In exchange, in good faith, the Company uses its discretion and experience in product development and regulatory affairs, its commercial resources and business savvy and, assuming that any relevant statutory, regulatory or administrative authorizations or permits for a vaccine product are obtained, its marketing, sale and distribution savvy for the benefit of both Parties."
— SEC 2010
"BPS is a party to a license agreement dated May 4, 2010, or the Canada License, with the Her Majesty the Queen in Right of Canada, or Canada. The Canada License grants BPS a worldwide, personal, non-transferable, sole, revocable, royalty-bearing license for commercialization of specified Canada patent rights relating to technology based on rVSV. The license is subject to Canada's retained right to use the Canada patent rights and technology to improve the patent rights, carryout educational purposes, and development of the patent rights where BPS cannot obtain regulatory approval or meet demand. BPS may grant sublicenses under the Canada license, provided that each sublicense is consistent with the terms and conditions of the Canada License and contain certain mandatory sublicensing provisions. In consideration of the license grant, BPS must pay to Canada a specified patent and signing fees, annual license maintenance fees, patent prosecution costs, potential milestone payments in an aggregate amount up to approximately C$205,000 per licensed product, and royalties as a low single-digit percentage of the sales price of the licensed products sold by BPS, which royalty rate varies depending on the type of licensed product. In addition, if BPS grants a sublicense under the licenses granted by Canada, BPS is required to pay to Canada a percentage of certain consideration BPS receives from the sublicensee. BPS is obligated to use commercially reasonable efforts to develop and market the licensed products. If BPS breaches its obligations and fails to cure the breach, Canada may terminate the Canada License. Unless terminated earlier, the Canada License will remain in effect until the expiration of the last of the Canada patent rights. Pending the status of certain patent applications and the payment of appropriate maintenance, renewal, annuity or other governmental fees, we currently expect the last patent will expire under this agreement in 2023, excluding any patent term adjustments or patent term extensions or additional patents issued that are included under the license. Canada may terminate this agreement for BPS's failure to use commercially reasonable efforts to commercialize, failure to pay, breach of confidentiality, cessation of business, criminal conviction or other breach of its obligations under the agreement. BPS may not assign the Canada License to a third party without the prior written consent of Canada, not to be unreasonably withheld. This agreement will terminate automatically if BPS assigns the Canada License without prior written consent or if BPS files for bankruptcy or similar proceedings."
— SEC 2011
"These are all experimental drugs that have not met the requirements … even for a Phase 1 [trial] right now in humans. So they have to pass all the toxicity [tests], they have to pass the safety trials."
— Dr. Kobinger July 2014
"NewLink Genetics Corporation, through its wholly owned subsidiary, BioProtection Systems Corporation announced that they had secured a letter contract with the United States Defense Threat Reduction Agency (DTRA) for studies that will bring an Ebola vaccine licensed from the Public Health Agency of Canada closer to human clinical trials. The letter contract is for $1.0 million with additional funding subject to final negotiation and will fund Investigational New Drug (IND)-enabling pre-clinical toxicology studies and includes the manufacture of clinical materials."
— Marketwired 2014
"...an urgent need for a medical countermeasure against the deadly Ebola virus...This Ebola vaccine has been 100% effective in preventing lethal infection when given to non-human primates before they are infected with the virus. The vaccine also acts rapidly enough to have significant efficacy even when given to animals that have recently received a typically lethal dose of Ebola virus."
— Charles Link CEO 2014
In the same announcement NewLink President and Chief Medical Officer, Nicholas Vahanian noted that there was an,
"Advancing this vaccine into a human Phase I safety study is a major priority for NewLink and our partners, whose ongoing support will be critical for moving the project forward."
— Vahanian CFO 2014
vaccine developed by Canadians, is being donated to the WHO by the Canadian government "for use in the West African outbreak response." [1] NewLink, a partner with Canada, is also working “around the clock” to start trials. NewLink president Nicholas Vahanian said in a telephone interview with Bloomberg journalists that they has reserved enough of the vials for human trials "and made a joint decision with the Canadian government to donate the rest." [10]
{{
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link)"This vaccine is intended to be used in Phase I clinical trials, to start in late October or early November. This will determine if the vaccine is safe to use in humans and if so, determine the appropriate dosage. The WHO has recruited 250 volunteers ready to begin clinical trials in four locations: Switzerland, Germany, Gabon and Kenya. If results of this and following trials are positive, the deployment of this vaccine in environments such as West Africa would be facilitated by the expected requirement of only a single dose. Also, its effectiveness in nonhuman primates when administered even after exposure to the virus could help to protect health-care workers after a suspected exposure."
In response to concerns about perceived delays in testing and manufacturing on the part of his company NewLinks, Charles Link explained that NewLink succeeded in the almost impossible task of getting through regulatory requirements in record time. [31] "The vaccine is now being tested on human subjects in five separate trials, including one in Halifax. The company has been clearing very challenging regulatory hurdles with unprecedented speed... To get the trials going in the space of about 10 days, a team of people working 16 to 18 hours a day, through the week, through the weekend,” managed to get FDA approval within four days." [31]
President of Merck Vaccines, Julie Gerberding, said, [7]
", "Merck is committed to applying our vaccine expertise to address important global health needs and, through our collaboration with NewLink, we hope to advance the public health response to this urgent international health priority."
— Julie Gerberding 2014
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Category:Hemorrhagic fevers Category:Viral diseases