Sophia Zhao

Using the groundwork laid by Yale scientists in the 1990s, the pharmaceutical company Merck & Co. received approval from the European Commission for the first-ever Ebola vaccine on Nov. 11.

The vaccine’s approval is the fruition of decades of research led by John Rose, a School of Medicine pathology professor emeritus who developed a method to genetically engineer the harmless vesicular stomatitis virus, or VSV, to express proteins found on other viruses to build immunity without developing harmful symptoms.

“This was an eight-year endeavor in my lab at Yale,” Rose said. “We suspected that VSV, which is a type of RNA virus circulating among livestock that is harmless to humans, could be a very potent vaccine platform for numerous diseases, like influenza and HIV. The idea was to insert new genes from pathogens into VSV and use this genetically modified virus as a vaccine.”

When injected, the genetically modifiable virus developed by Rose’s group allows exposure to disease-causing proteins from a range of harmful viruses while circumventing illness. The body is then able to build immunity to the harmless “mimickers” of infection.

In the case of Ervebo — the name of the vaccine — immune cells respond to Ebola surface proteins built onto VSV, and immunological memory can develop without making people sick because the VSV system poses no harm.

According to Rose, the genetically engineered VSV platform was not intended for treating a specific disease, but rather to be modified for applications in numerous viral diseases. After developing the VSV platform, Rose and his collaborators provided this system to over 100 labs, including one in Germany working on an Ebola vaccine.

With several ongoing interdisciplinary collaborations involving the VSV platform, an HIV vaccine utilizing genetically modified VSV began clinical trials in 2011, and research is underway for a Zika virus vaccine using the VSV platform, Rose said.

“It’s likely that there will be other VSV vaccines in the future,” said Helen Branswell, public health and infectious diseases reporter at STAT News. “A lot of scientific groups have been working with this platform to see if they can develop vaccines for different diseases, and this is the first time a vaccine using this platform has been approved.”

The groundwork laid by Rose and his collaborators became the earliest step in the development of the Ervebo. The vaccine — acquired by Merck in 2014 from a small biotech company called NewLink Genetics — has been instrumental in limiting the Ebola epidemic in sub-Saharan Africa even prior to its approval.

“This vaccine has been in use in the outbreak in the Democratic Republic of [the] Congo for the past 16 months,” Branswell told the News. “It’s been used under the legal umbrella of ‘compassionate use.’”

The vaccine was administered to patients under a compassionate use principle, also known as expanded access, that enables access to promising but not yet fully characterized therapies when no other treatments exist. After the vaccine’s successful phase III clinical trials during the West African outbreak, Ervebo has been used under this legal umbrella to vaccinate more than 250,000 people in the most recent outbreak.

“The European Commission’s marketing authorization of Ervebo is the result of an unprecedented collaboration for which the entire world should be proud,” said Ken Frazier, Merck’s chairman and chief executive officer, in a press release at the time of approval.

While there is no approved treatment that neutralizes the Ebola virus after infection, scientists are developing a range of immunological and pharmacological therapies for the disease.

According to the World Health Organization, the ongoing Ebola outbreak that started in the Democratic Republic of Congo in Aug. 2018 has seen a 67 percent fatality rate.

Viola Lee | kyounga.lee@yale.edu

Correction, Dec. 5: An earlier version of the article erroneously stated that the vaccine was acquired by Merck in 2013 from Canadian and German researchers. However, the vaccine was actually acquired in 2014 from a small biotech called NewLink Genetics, which had acquired it from the Canadian government following a collaboration between German and Canadian researchers at the Canadian National Microbiology Laboratory. Additionally, an earlier version of the article stated that the 2018 Ebola outbreak had a fatality rate of 61 percent. In fact, there were two Ebola outbreaks in 2018 in the Democratic Republic of Congo, of which the earlier outbreak had a fatality rate of 61 percent. The ongoing Ebola outbreak, which is the outbreak in which more than 250,000 doses of vaccine have been used, started in August 2018, and has had a fatality rate of 67 percent.