PROVIDENCE – New recipes for a vaccine to combat the H7N9 flu went into production this weekend, in a collaboration between EpiVax and Aldevron in Fargo, N.D., and a researcher at Fort Detrick, Md., the home of the Army Medical Research Institute of Infectious Diseases, according to Dr. Anne S. De Groot, chief science officer and CEO of EpiVax, a bioscience firm based in the Knowledge District.
“The goal is to produce enough vaccine to do a proof in principle study,” De Groot told the Providence Business News. “At Aldevron, they will be manufacturing a DNA vaccine that can be used to immunize mice that are subsequently challenged with the virus.”
At Fort Detrick, she continued, the work will be focused on developing a vaccine that can be employed by an FDA-approved delivery system currently used to deliver anti-bacterial products in food, such as the anti-listeria product used in cheese. “Our vaccines are platform independent,” she said.
The accelerated production schedule was prompted by news from China about the increasing spread of H7N9 infection: confirmed cases in the last two weeks have climbed from 3 to 60 with 13 deaths, with two cases of human-to-human transmission and with more than 1,000 people being “watched,” according De Groot, who has been monitoring reports from scientists and from the World Health Organization. One new case of H7N9 was reported in Beijing on April 12, indicating that the flu is spreading.
“More worrisome is the fact that these [cases] are far apart [geographically],” De Groot said. “Either human-to-human transmission is occurring, or there is an animal vector. The death rate is running about 30 percent.”
De Groot’s work has gained traction with one of the world’s leading flu researchers, Dr. Richard J. Webby, director of the WHO Collaborating Center for Studies on the Ecology of Influenza in Animals and Birds. Webby is one of the research scientists who has received an isolated virus copy of the H7N9 flu to study and develop a vaccine response.
In a email sent on April 14 to De Groot, Webby asked her for suggestions on how to engineer changes that will increase T cell epitopes within the HA [hemagglutinin] protein, creating a hybrid approach to the manufacture of the vaccine.
“Just about to hop on plane for Europe,” Webby wrote. “Got any good ideas about HA changes we should engineer in that will increase T cell epitopes without altering [the] binding sites? We have HA and NA cloned and can easily put some in to see.”
De Groot said her team would be producing a three-dimensional model of the H7N9 flu protein, enabling Webby to introduce “much better epitopes” into the traditional vaccine design.
De Groot said Webby’s hybrid approach was “a brilliant idea,” because he would be manufacturing an improved vaccine using the HA approach and incorporating De Groot’s “better epitope” strategy. “More people will be comfortable with that approach,” she said.
One reason for De Groot’s heightened urgency were the results of her team at EpiVax’s analysis of the H7N9 sequencing, which found it to be “low immunogenicity” – the ability to provide an immune response in the body of a human or animal. “When I heard this from the team [Friday] morning, I was immediately very worried,” De Groot said, because the immunogenicity factor was lower than previous circulating viruses. “This means [it is] harder to make an effective vaccine, and harder to make a diagnostic test that will be cheap enough to use.”
As a result of these difficulties, De Groot has labeled the H7N9 a “stealth virus,” and expressed frustration about the inability to get the attention of leadership at the Centers for Disease Control and Prevention or the National Institutes of Health.
Through an intermediary, EpiVax reached out to Nancy J. Cox, director of the Influenza Division at the CDC. Cox also directs the CDC’s World Health Organization Collaborating Center for Surveillance, Epidemiology and Control of Influenza. But, unlike Webby, Cox’s office declined to speak directly with De Groot.
“They basically said, ‘You know, we’re familiar with EpiVax, but we’re going to continue with the FDA-approved approaches. … It’s what we are comfortable with,’” De Groot said, voicing her exasperation.
“When something like a new pandemic is emerging, it’s time to think differently. The time to do that is now,” De Groot said. Because of the low immunogenicity factor of the H7N9 flu virus, she continued, “There will be no antibody response unless you make the vaccine the way we make them, with epitopes that will drive an immune response. And we can make that vaccine really quickly. But I cannot get the attention of the CDC and the NIH.”
In China, De Groot continued, “the virus already has mammalian signatures, with widespread transmission in China from animals. Chinese health authorities should be vaccinating poultry workers.” Instead, she said, China is killing its poultry to try and contain the spread of the flu. “China’s the biggest poultry producer in the world; it will have a major impact on the economy in China, and globally,” De Groot said.
Chinese health officials have been trying to remain calm on the surface, De Groot continued. “In reality, it is nuts over there.”
According to a Reuters story posted on April 12, “In a bid to calm public jitters over the virus, Chinese authorities have detained a dozen people for spreading rumors about the spread of bird flu.” The story continued: “The new virus has been severe in most of the people affected, leading to fears that if it becomes easily transmissible, it could cause a deadly influenza pandemic, though there has been no indication of that happening.”
The story has been slow to break here in the United States, but that may be changing, according to De Groot, who said she would be interviewed Monday morning by both NPR and the BBC.
When asked about the capability of the Rhode Island health care delivery system to cope with a major flu pandemic, De Groot responded: “People are taking their information from the CDC, and that is like the blind leading the blind,” De Groot said. “If past pandemics are any indication, it may take the CDC six months to make enough flu vaccine.” And, she added, “It may not be effective.”
