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Branswell’s “History and Application of Vaccines”

Helen Branswell’s article on the development, testing, and rollout of the Ebola vaccine details the challenges and breakthroughs achieved by various individuals and teams involved in its manufacturing. According to the article, Gary Kobinger worked on an Ebola vaccine but had not conducted human trials when the 2014 Ebola broke out in West Africa (Branswell). Although the World Health Organization (WHO) rejected Kobinger’s offer at the onset of the outbreak, the quick spread of Ebola across Guinea, Liberia, and Sierra Leone necessitated the vaccine’s rollout (Branswell). Originally known as rVSV-ZEBOV, the Ebola vaccine could not be manufactured due to the sporadic nature of outbreaks which meant that it lacked rigorous testing grounds and pharmaceutical companies could not recover their production costs.

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John Jack Rose began developing the Ebola vaccine in the 1990s by using the livestock vesicular stomatitis virus (VSV) as the backbone because it infected people without sickening them and caused a rapid response that produced surprisingly high antibody levels. First, Rose and his team added an influenza virus protein on VSV and tested it on mice, making fast responses that completely protected the mice on a single dose. The VSV always worked as a backbone for other viruses, including SARS, bird flu, Zika, and measles (Branswell). Although Rose did not test out the Ebola virus, he shared his construct with over 100 labs worldwide. One of the labs in Marburg, Germany, began to study Ebola genes and the related Marburg virus in the late 1980s under Hans-Dieter Klenk’s leadership (Branswell). The team used lower biocontainment levels for safety and affordability to place Ebola and Marburg proteins on the VSV backbone. Although the group considered developing the respective vaccines, they lacked high containment labs to conduct animal tests.

Klenk’s student, Heinz Feldmann, moved to a newly built lab in Canada, which had biosafety level 4 facilities that could support Ebola studies. However, Feldmann did not think of developing an Ebola vaccine until Gary Nabel mentioned that the Ebola’s glycoprotein caused devastating damage to the infected people and animals (Branswell). Feldmann set out to prove that Nabel’s argument was invalid by infecting mice with Ebola glycoprotein on the VSV backbone: the protein did not harm the mice. The team then decided to expose the mice to Ebola. They were unharmed, triggering the unit to expose another group that was not infected with the VSV with Ebola glycoprotein. The latter group died from Ebola, and that became the beginning of the Ebola vaccine project. Feldmann’s friend, Tom Geisbert, tested the VSV on primates and monkeys exposed to the rVSV-ZEBOV survived Ebola, leading to publishing on this study in 2005 (Branswell). Although the report excited scientists, nobody was interested in Ebola due to its inability to generate enough pharmaceutical companies’ excitement.

The need for rVSV-ZEBOV emerged in 2009 when a German researcher pricked her finger with an Ebola needle, and field workers and researchers agreed to give her the vaccine. She was vaccinated 48 hours after the accident, developed a fever the next day, and recovered by the third day. Although it was not established whether she had been infected, it was clear that the vaccine did not cause humans harmful side effects. The vaccine development got a $2 million funding from the United States government, helping it patent the vaccine system and partnered with NewLink Pharmaceuticals for production purposes (Branswell). Initially, Newlink was to pay the patent holder $156,000 for each developed product, but it was increased to $360,000 after a few years. Nevertheless, NewLink was acquired, and the Ebola vaccine did not continue until the Ebola outbreak got out of control in 2014.

The WHO rejected vaccine offers based on a lack of human testing, but the Doctors Without Borders team pushed for adoption as the health situation deteriorated. When the WHO declared a healthy emergency, the Canadian government offered to donate its vaccine to save lives. The WHO agreed to use the vaccine only after phase I trials, conducted by Walter Reed Army Institute of Research (WRAIR) (Wolf et al. 1). Merck pharmaceutical company paid $50 million to NewLink for the license and closed the deal on Nov. 24, 2014 (Branswell). The trials used the ring vaccination technique to protect people who have been in contact with the infected and block its spreading. The placebo control was replaced with immediate and 21 days delayed vaccinations (Rappuoli et al.). By June 2015, the vaccine was declared to have worked, and Lancet published the report in the next month (Branswell). Today the vaccine is authorized by the European Commission and the FDA.

The article summarized above details the history and application of the Ebola vaccine. Essential connections with the text include the vaccine development process, including animal studies and clinical trials. The vaccine development process involves the exploratory stage, pre-clinical-stage, IND application, phase I trials, phase II trials, phase III trials, and post-licensure vaccines monitoring (Rappuoli et al.). The Ebola vaccine passed through these stages, but phase I, II, and III trials were criticized for how they were conducted (Wolf et al. 1). The vaccine was tested and rolled out simultaneously due to a medical emergency.

Works Cited

Branswell, Helen. “’Against all Odds’: The Inside Story of How Scientists across three Continents Produced an Ebola Vaccine.” STAT, 2020.

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Rappuoli, Rino, Steven Black, and David E. Bloom. “Vaccines and Global Health: In Search of a Sustainable Model for Vaccine Development and Delivery.” Science Translational Medicine, vol. 11, no. 497, 2019, doi: 10.1126/scitranslmed.aaw2888.

Wolf, Jayanthi, et al. “Applying lessons from the Ebola vaccine experience for SARS-CoV-2 and other epidemic pathogens.” npj Vaccines, vol. 5, no. 1, 2020, pp. 1-5, doi: 10.1038/s41541-020-0204-7.

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