doi: 10.1128/JVI.00363-18. (An amendment a couple of years later would increase that amount to roughly $360,000.) The pharmaceutical industry was not interested in making a product to protect against a disease that emerged only now and again in impoverished countries. Since Ebola virus was first identified in 1976, sporadic outbreaks have been reported in Africa. The vaccine's manufacturer, Merck, Sharpe & Dohme, this year received Breakthrough Therapy Designation from the United States Food and Drug Administration and PRIME status from the European Medicines Agency, enabling faster regulatory review of the vaccine once it is submitted. With or without vaccination, it is critical to implement appropriate infection control and prevention measures as part of efforts to prevent the spread of EVD. Bethesda, MD 20894, Web Policies mRNA production is cell-free, using in vitro transcription methodology. At first, the protein on the surface of the VSV virus known as the glycoprotein or G protein was swapped out and replaced with the Ebola glycoprotein. The site is secure. In case of Ebola flare-ups prior to approval, access to the vaccine is being made available through a procedure called compassionate use that enables use of the vaccine after informed consent. As researchers who conducted the Phase 1 and Phase 2 trials crunched their data, others were planning pivotal Phase 3s. They're even trying them for non-infectious diseases like cancer. Proper Name: Ebola Zaire Vaccine, Live Tradename: ERVEBO Manufacturer: Merck Sharp & Dohme Corp. The idea was that the harmless virus would teach the immune system to recognize harmful potential invaders. You know, when things go really wrong, quite often its a succession of little issues in which none by themselves could have derailed the train. In addition to showing high efficacy among those vaccinated, the trial also shows that unvaccinated people in the rings were indirectly protected from Ebola virus through the ring vaccination approach (so called "herd immunity"). 2013 Dec 19;7(12):e2600. Back in Canada, Kobingers offer to the WHO had been rebuffed. Once allowed to dry, the patches can be stored at room temperature . Suder E, Furuyama W, Feldmann H, Marzi A, de Wit E. Hum Vaccin Immunother. Krhling V, Erbar S, Kupke A, Nogueira SS, Walzer KC, Berger H, Dietzel E, Halwe S, Rohde C, Sauerhering L, Arago-Santiago L, Moreno Herrero J, Witzel S, Haas H, Becker S, Sahin U. Mol Ther. But realistically, it was a nonstarter. The first mRNA vaccines using these fatty envelopes were developed against the deadly Ebola virus, but since that virus is only found in a limited number of African countries, it had no commercial development in the U.S. Then COVID-19 hit what happened then? On rare occasions, people become sick with EVD after coming into direct contact with infected animals, which can then lead to EVD outbreaks when the virus spreads between people. NIAID and Okairos (a company later acquired by GSK) developed an Ebola vaccine candidate (now licensed to the Sabin Vaccine Institute) that uses a chimpanzee adenovirus (cAd3) vector, or carrier, to deliver Ebola genetic material. But fever could also have been the first symptom of an Ebola infection. An official website of the United States government, Recalls, Market Withdrawals and Safety Alerts, First FDA-approved vaccine for the prevention of Ebola virus disease, marking a critical milestone in public health preparedness and response. Johns Hopkins Bloomberg School of Public Health615 N. Wolfe Street, Baltimore, MD 21205, , is the Desmond M. Tutu Professor of Public Health and Human Rights and director of the, Center for Public Health and Human Rights. From a regulatory perspective, it matters a lot.. Would you like email updates of new search results? Mobile biocontainment unit used to monitor a German researcher who had pierced her finger with a syringe containing Ebola virus during an experiment in 2009. This is followed by vomiting, diarrhea, rash, impaired kidney and liver function and in. So, what happened once they figured out this technology? Scientists from the Centers for Disease Control and Prevention were to test the vaccines in Sierra Leone. In March 2022 Moderna announced the development of mRNA vaccines for 15 diseases: Chikungunya virus, COVID-19, Crimean-Congo haemorrhagic fever, Dengue, Ebola virus disease, HIV, Malaria, Marburg virus disease, Lassa fever, Middle East respiratory syndrome coronavirus (MERS-CoV), Nipah and henipaviral diseases, Rift Valley fever, Severe fever Feldmann and Geisbert, an Ebola expert who was then at the U.S. Army Medical Research Institute of Infectious Diseases, thought Nabel was wrong and that they could use the VSV construct to prove it. It is widely considered to be unethical to use untested drugs or vaccines in Africa, where clinical safeguards are sometimes lacking and where memories linger of scandals like Pfizers use of a meningitis drug that resulted in the death of 11 children in 1996. Still, Kobinger saw a bright side: The seed of the [vaccine] being available was planted.. Recent advances in the development of vaccines for Ebola virus disease. Rose thought the virus could be an effective backbone for a vaccine if it could be engineered to include genes of viral pathogens like influenza or HIV. The only thing in our mind was that we wanted to assess if the vaccine worked or not because we wanted to contribute if possible to find a solution, Diallo told STAT via email. The vaccine candidate combines the Ad26.ZEBOV vector (based on the AdVac platform developed by Crucell Holland B.V., a company acquired by Janssen Pharmaceutical Companies of Johnson & Johnson) with a modified vaccinia virus Ankara (MVA)-vectored vaccine (MVA-BN Filo, developed by Bavarian Nordic). The .gov means its official.Federal government websites often end in .gov or .mil. ERVEBO (Ebola Zaire Vaccine, Live also known as V920, rVSVG-ZEBOV-GP or rVSV-ZEBOV) is approved by the U.S. Food and Drug Administration (FDA) for the prevention of disease caused by Ebola virus (EBOV; species Zaire ebolavirus) in individuals 18 years of age and older as a single dose administration. Todays approval is an important step in our continuing efforts to fight Ebola in close coordination with our partners across the U.S. Department of Health and Human Services, as well as our international partners, such as the World Health Organization. "Vaccines makers are trying mRNA technology for everything from influenza to RSV, to Ebola to herpes. NIAID has supported the development of various candidates, including the rVSV-ZEBOV vaccine developed by Merck. Once allowed to dry, the patches can be stored at room temperature . Ebola virus disease: Vaccines 11 January 2020 | Q&A Is there a vaccine against Ebola virus disease? Moderna's mRNA-1273, which entered into clinical trials just 66 days after SARS-CoV-2 was first sequenced, showcases the potential for nucleotide-based vaccines. Rose, nonetheless, thought a VSV Ebola vaccine, in theory, would work as well. A further trial for the vaccine is planned to commence in Tanzania by the end of 2021. Indication: ERVEBO is a vaccine indicated for the prevention of disease caused by Zaire. Klenk decided that ought to change. If Nabels theory was correct, exposure to the protein should have been toxic to the mice. The vaccine is the first to prevent infection from one of the most lethal known pathogens, and the findings add weight to early trial results published last year. The agency also is responsible for the safety and security of our nations food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products. Ebola outbreak in Uganda: how worried are researchers? The trial ultimately enrolled 1500 participants and results indicated that the vaccine was well-tolerated and induced an immune response among participants. Great article! Unauthorized use of these marks is strictly prohibited. It was ugly, Kieny said. 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. Two serious adverse events were judged to be related to vaccination (a febrile reaction and one anaphylaxis) and one was judged to be possibly related (influenza-like illness). 8600 Rockville Pike BARDA also is supporting advanced development of this candidate. Incredible mind, incredible heart: After decades fighting Ebola, a beloved expert hangs up his boots. 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. Yet given the scale of the expanding crisis, experts were now scouring the medical literature, looking for any existing medicines that could be repurposed to fight Ebola, or experimental vaccines or drugs, regardless of where they were in the developmental pipeline. What was happening in the interim? From 10 days after vaccination the time needed for the immune system to respond to the vaccine there were no cases among people who had been vaccinated in the early rings, but there were cases among the delayed vaccination rings. 2018 May 14;92(11):e00363-18. Prior to the pandemic, mRNA vaccines were primarily being developed to target a variety of cancers. In less than 12 months, 12 clinical trials running the gamut from a first in man dosing study to a Phase 3 efficacy trial had been conducted. The data and safety monitoring board recommended that health workers vaccinate anyone who had come in contact with people infected with Ebola as quickly as they could be found, rather than delaying some vaccinations. "While these compelling results come too late for those who lost their lives during West Africa's Ebola epidemic, they show that when the next Ebola outbreak hits, we will not be defenceless," said Dr Marie-Paule Kieny, WHOs Assistant Director-General for Health Systems and Innovation, and the studys lead author. However, the technology faces . The vaccine had worked. Saint-Pierre Contreras G, Conei Valencia D, Lizama L, Vargas Zuiga D, Avendao Carvajal LF, Ampuero Llanos S. Viruses. An Ebola vaccine was more than two decades in the making. 2023 Feb 1;31(2):374-386. doi: 10.1016/j.ymthe.2022.10.011. Self-amplifying RNA vaccine protects mice against lethal Ebola virus infection. They are effective, safe, and can be produced in large quantities. Phase 3 trials for Ebola vaccines could start in early 2015 with initial safety data possibly available by June 2015. No one outside the lab realized that the vaccine being tested in people was not identical to the one that had been studied so thoroughly in animals. On Aug. 8, 2014, the WHO declared the outbreak a global health emergency. That was true, he added. In June, however, the trials data and safety monitoring board concluded there were not likely to be enough additional cases to change the outcome of the study. The outbreak, which probably started in late 2013, smoldered in the way Ebola outbreaks do. It is known as Ervebo. Epub 2018 Jun 18. The company started fielding approaches from the WHO, the Biomedical Advanced Research and Development Authority (BARDA), and others asking if Merck would step up. NewLink agreed to pay the Canadian government which officially held the patent about $156,000 for each product it developed. But thats not proof, of course, said Kieny of the WHO. 2023 Jan 26;11(2):268. doi: 10.3390/vaccines11020268. The list of potential white knights wasnt long. Mire CE, Geisbert JB, Marzi A, Agans KN, Feldmann H, Geisbert TW. The FDAs approval of Ervebo is a major advance in helping to protect against the Zaire ebolavirus as well as advancing U.S. government preparedness efforts. Print 2018 Jun 1. At the time, Ebola had killed about 1,300 people over the nearly 30 years since it had been discovered. Following vaccination, participants will be monitored through several visits over a six-month period, with results expected in the second quarter of 2022. Yes, it was exciting, but where would you go with that excitement? Feldmann said when asked about the results. Dr. Abdourahmane Diallo, a public health physician who works for Guineas health ministry, was one of those who answered the WHOs appeal for help. An experimental Ebola vaccine was highly protective against the deadly virus in a major trial in Guinea, according to results published today in The Lancet. If two assets hadnt come researchers way, its almost a certainty that Ervebo would have never come to fruition. NIAID and WRAIR are conducting a clinical trial examining the safety and dosage of an investigational vaccine designed to protect against Sudan virus (known as cAd3-EBO S) at Makerere University in Kampala, Uganda. This is a brilliant story. "Ebola left a devastating legacy in our country. Already, mRNA vaccines are being tested for other infectious agents, such as Ebola, Zika virus, and influenza. The Canadian government agreed to send the vaccine which was not human-grade product, but material the lab had produced for animal studies. The PREVAIL findings indicated the vaccine was well-tolerated and induced an immune response in recipients. A victory for never giving up ! An outbreak in three West African countries (Guinea, Liberia and Sierra Leone) from 2014 to 2016 resulted in more than 28,000 cases of EVD and more than 11,000 deaths that were caused by Zaire ebolavirus. When autocomplete results are available use up and down arrows to review and enter to select. The vaccine ink is made up of lipid nanoparticles containing mRNA vaccine molecules, as well as a polymer similar to sugar water. 12-14 Clinical chemical analyses of plasma samples that had been separated. There were hints that it was working, he remembered. Significance of Preexisting Vector Immunity and Activation of Innate Responses for Adenoviral Vector-Based Therapy. Google Scholar. On Dec. 21, the FDA approved the vaccine in the United States. Thank you for recounting this important news event. We concur that, taken together, the results suggest that the vaccine most likely provides some protection to recipients possibly substantial protection, as stated in the preliminary report, the authors wrote. 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. And sometimes for something good to happen its the same, she said. Ebola Virus Disease Vaccines: Development, Current Perspectives & Challenges. Experience with ChAdOx1 nCoV-19 (Oxford-AstraZeneca COVID-19 vaccine) has shown the vaccine can be rapidly manufactured at high volume for low cost, with storage conditions amenable to use in the developing world. Theres a big gap between when the first mRNA flu vaccine was tested in mice in the 1990s and when the first mRNA vaccines for rabies were tested in humans in 2013. The University of Oxford have begun recruiting for a Phase I trial to test an Ebola vaccine in human volunteers with the first vaccinations having already taken place. Onset of symptoms of EVD can be sudden and can include fever, fatigue, muscle pain, headache and sore throat. You can view all news or browse by category, Illustration showing how the Ebola virus looks under a microscope, ProspectiveContinuing Educationstudents, Prospective online/distance learning students. official website and that any information you provide is encrypted It, too, was turned down. A DNA-based vaccine developed by scientists at NIAID's Vaccine Research Center (VRC). While the risk of Ebola virus disease in the U.S. remains low, the U.S. government remains deeply committed to fighting devastating Ebola outbreaks in Africa, including the current outbreak in the Democratic Republic of the Congo, said Anna Abram, FDA Deputy Commissioner for Policy, Legislation, and International Affairs. Two U.S. Food and Drug Administration (FDA)-approved mRNA vaccines for COVID-19 have saved millions of lives. The FDA granted this application Priority Review and a Tropical Disease Priority Review Voucher under a program intended to encourage development of new drugs and biologics for the prevention and treatment of certain tropical diseases. A planned sample of 26 participants who must be assessed as healthy and aged 18 to 55 will all receive one dose of the ChAdOx1 biEBOV vaccine at the University. Roughly 48 hours after the accident, the woman, who was not publicly identified, was vaccinated. I guess that was basically the start of the vaccine project, even though I dont think we really jumped on it with a lot of priority right away, said Feldmann. The RNA sequence used in the COVID-19 vaccine developed by Pfizer and . The following day, she developed a fever. The strategy is similar to the VRC's investigational flavivirus vaccine for West Nile virus infection. An official website of the United States government. The government in Guinea was also keen to host a trial. But somewhere along the line, a key feature in the vaccine had been changed. It was there, in 1967, that laboratory workers and people related to them became sick with what was later named the Marburg virus. This became the Canadian vaccine how it was known for many years. Postdoctoral fellowship in vascular biology at UT Southwestern, studying the endothelial basis of cardiometabolic disease. By the end of March, one of Guineas neighbors, Liberia, was investigating possible cases. Others agreed. Virus Res. Before HHS Vulnerability Disclosure, Help Moderna, which is based in Cambridge, Massachusetts, is close to securing a deal to develop an mRNA vaccine against Ebola and other filoviruses, according to news agency Bloomberg. But the number of people enrolled was limited, and no vaccine works every single time. NIAID and the Walter Reed Army Institute of Research (WRAIR) evaluated rVSV-ZEBOV in Phase 1 clinical trials which showed rVSV-ZEBOV is safe and able to induce a robust immune response in recipients. Summary Postdoctoral Research Associate-Cell Biology of Neural Development St. Jude Childrens Research Hospital St. Jude Childrens Research St. Jude Children's Research Hospital (St. Jude). In principle, mRNA vaccines have several advantages over conventional vaccines. Volunteers interested in enrolling on the study can do so online. I always had to defend it, and we always were scrambling for money, he said. Confirmed outbreaks of EVD have been documented since the 1970s, primarily in areas of sub-Saharan Africa, where scientists believe the virus is always present at low levels in certain infected wild animals. The vaccine is a replication-competent, recombinant vesicular stomatitis virus-based vaccine that protects only against Ebola virus (species Zaire ebolavirus ). Currently there are no licensed vaccines to prevent Ebola virus disease. To see if the system worked, his group added a protein from an influenza virus to VSV and injected it into mice. Hundreds of scientists had worked on mRNA vaccines for decades before the coronavirus pandemic brought a breakthrough. Non-replicating viral vector vaccines, while a relatively recent approach, have been studied extensively in HIV and other disease trials. The mRNA technology transfer programme, comprising a consortium of biomanufacturing partners from 15 countries, saw the launch of its technology transfer hub in Cape Town this week, and the kick . Prompted by Sprecher, MSF started pushing for use of the VSV vaccine. Can children, pregnant and breastfeeding women be vaccinated? The mRNA vaccine technology also is being tested as a treatment for cancer. It was about the vaccine being used in the trials, donated by the Canadian government. After hed moved to the Canadian lab, though, Feldmann and Tom Geisbert, a friend and frequent collaborator, heard Dr. Gary Nabel, then head of the National Institutes of Healths Vaccine Research Center, deliver a lecture on Ebola. Ebola virus disease is a rare but severe and often deadly disease that knows no borders. Roses lab and others later used VSV as a backbone for experimental vaccines for bird flu, measles, SARS, Zika, and other pathogens. The Winnipeg lab also had been working for years on an Ebola vaccine, one that looked tremendously effective in animal models. doi: 10.1371/journal.pntd.0002600. The vaccine candidates currently making headlines use mRNA and vector-based platforms. Kieny waxed a bit philosophical about the unlikely success of rVSV-ZEBOV. Milligan ID, Gibani MM, Sewell R, Clutterbuck EA, Campbell D, Plested E, Nuthall E, Voysey M, Silva-Reyes L, McElrath MJ, De Rosa SC, Frahm N, Cohen KW, Shukarev G, Orzabal N, van Duijnhoven W, Truyers C, Bachmayer N, Splinter D, Samy N, Pau MG, Schuitemaker H, Luhn K, Callendret B, Van Hoof J, Douoguih M, Ewer K, Angus B, Pollard AJ, Snape MD. Because of the public health importance of a vaccine to prevent EVD, the FDA worked closely with the company and completed its evaluation of the safety and effectiveness of Ervebo in less than six months. Both the template and transcript can be produced in the laboratory using materials that are readily accessible. Some testing in animals had shown it had increased survival when given after exposure, even as late as 48 hours afterward though whether that translated into a similar effect in people was unclear. It was a pivotal moment, but it also created a conundrum. To date, more than 250,000 individuals participating in clinical trials and vaccination initiatives have received at least the first dose of the Johnson & Johnson Ebola vaccine regimen, including . There was no potential for drug makers to recoup development costs; and, with outbreaks only sporadic, there was little opportunity to subject experimental vaccines to rigorous tests. NIAID also is part of an international consortium conducting an ongoing clinical trial of various vaccine regimens using rVSV-ZEBOV and another experimental prime-boost regimen known as Ad26.ZEBOV/MVA-BN-Filo. Cancerous cells create unique pieces of protein that are not found on healthy cells. Get the most important science stories of the day, free in your inbox. Quite frankly, from a scientific prospective, it doesnt matter, agreed Kobinger. NIAID is sponsoring the study, called HVTN 302, and the NIAID-funded HIV Vaccine Trials Network (HVTN . The vaccine platform was initially developed in the early 1990s, in an effort to create safe and effective vaccines in a pandemic situation. When IDT had produced vaccine, it shipped back vials to Alimonti who ran the tests to ensure the material was pathogen-free. Alimonti, who died of cancer in 2017, loved the project. In place of a placebo control, the rings were randomly assigned to either immediate vaccination, or vaccination after a 21-day delay. This study will test the safety of an experimental vaccine developed to protect against Ebola virus infection and to determine if the vaccine induces an immune response to the virus. Epub 2022 Oct 27. mRNA vaccines have elicited potent immunity against infectious disease targets in animal models of influenza virus, Zika virus, rabies virus and others, especially in recent years, using. A woman gets vaccinated at a health center in Conakry in March 2015 during the Guinea clinical trial of the rVSV-EBOV vaccine. Her former colleagues describe her as the unsung hero of the Ebola vaccine. the courage and conviction of the researchers is truly admirable. The needle penetrated three layers of gloves; though the wound didnt draw blood, her skin had been punctured. Access Nature and 54 other Nature Portfolio journals, Get Nature+, our best-value online-access subscription, Receive 51 print issues and online access, Get just this article for as long as you need it, Prices may be subject to local taxes which are calculated during checkout, doi: https://doi.org/10.1038/d41586-022-03590-y. Unlike some viral vaccines, mRNA does not integrate into the genome, obviating concerns about insertional mutagenesis5. The reality was that, for years, scientists who studied Ebola, which belongs to a family of viruses called filoviruses, had poured their hearts into work to develop vaccines and drugs to combat these deadly scourges. A roundup of STAT's top stories of the day. FOIA The WHO convened a meeting to determine the best path forward. As an afterthought, the group decided to expose the mice to Ebola to see what would happen. NIAID has supported the development of various candidates, including the rVSV-ZEBOV vaccine developed by Merck. Introduction: Ebolaviruses are non-segmented negative-strand RNA viruses in the Filoviridae family that cause a neglected infectious disease designated as Ebola virus disease (EVD). The grant was doled out by a Canadian defense program that funded research into tools to combat bioterrorism. No major pharmaceutical company had expressed interest in developing it. Before the week was out, cases were reported in Guineas capital, the first time Ebola had taken root in an urban setting. The design and manufacturing of mRNA-based vaccines on a clinical scale is possible within weeks from the time the antigenic sequence becomes available. The neutralizing antibody responses were fast and off the charts, he said. The special pathogens team at the Canadian lab joined the search to try to determine what was causing the new illness and how to contain it. The rapid development of rVSV-EBOV contributed to the development of WHOs R&D Blueprint, a global strategy to fast-track the development of effective tests, vaccines and medicines during epidemics. He recalled that his colleagues were excited at the prospect of taking part in the study. GSK was racing to test its own experimental Ebola vaccine. When Ebola broke out in Equateur province in the Democratic Republic of the Congo in the spring of 2018, the country agreed to use the vaccine under a compassionate use protocol similar to the protocol used in a clinical trial when there is no approved therapy. The first mRNA vaccines using these fatty envelopes were developed against the deadly Ebola virus, but since that virus is only found in a limited number of African countries, it had no commercial development in the U.S. None (Open Label) Primary Purpose: Prevention. The study will assess the immune response and safety of the new vaccine against the Zaire and Sudan species of . Vaccination is essential to help prevent outbreaks and to stop the Ebola virus from spreading when outbreaks do occur, said Peter Marks, M.D., Ph.D., director of the FDAs Center for Biologics Evaluation and Research. Today, the most advanced EVD vaccine approaches target EBOV and multiple phase 1-4 human trials have been performed over the past few years. Messenger RNA, or mRNA, was discovered in the early 1960s; research into how mRNA could be delivered into cells was developed in the 1970s. I live in the West Indies and I continued to follow the updates on Ebola. Can the vaccine cause adverse effects? The vaccine was licensed to NewLink Genetics, who in turn licensed it to Merck & Co. He and the team he led had a well-deserved reputation for their work on Ebola and other viral hemorrhagic fevers; Kobinger himself had led development of a promising Ebola therapy. The rVSV-ZEBOV trial is funded by WHO, with support from the Wellcome Trust; the UK Government through the Department for International Development; the Norwegian Ministry of Foreign Affairs; the Norwegian Institute of Public Health through the Research Council of Norway,; the Canadian Government through the Public Health Agency of Canada, Canadian Institutes of Health Research, the International Development Research Centre, and the Department of Foreign Affairs, Trade and Development; and Mdecins Sans Frontires. We have designed our new vaccine to target the two species of virus that have caused nearly all Ebolavirus outbreaks and deaths, and now look forward to testing this in phase I clinical trials.. A vaccine that produces those pieces can educate the immune system to . Recommendations made by the ACIP are reviewed by the CDC . In January, GAVI, the Vaccine Alliance provided US$5 million to Merck towards the future procurement of the vaccine once it is approved, prequalified and recommended by WHO. FDA approves an Ebola vaccine, long in development, for the first time. The source: primates imported for research purposes. The trial was led by WHO, together with Guineas Ministry of Health, Medecins sans Frontieres and the Norwegian Institute of Public Health, in collaboration with other international partners. The US government didnt throw billions of dollars into this vaccine. The FDA is committed to continuing our work across the U.S. government and with our international partners to prevent future Ebola outbreaks and mitigate the current outbreak in the DRC, reflecting our nations commitment to preparing for and responding to biological threats, like Ebola.. The gene inserts express an Ebola virus protein designed to prompt the human body to make an immune response. The research approach used to study the effectiveness and safety of this vaccine was precedent-setting during a public health emergency and may help create a model for future studies under similar circumstances.

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