By Sarah Ovaska
A team of Duke University doctors and researchers are racing to stop – or at least dull – the deadly rampage of the influenza virus, a pathogen that claims the lives of between 12,000 and 61,000 Americans annually.
The Duke Human Vaccine Institute, emboldened with up to $400 million in federal grants over the next seven years, is playing a key role in the development of a universal flu vaccine. It’s a feat that, if realized, could save thousands, or even hundreds of thousands, of lives going forward.
Though currently overshadowed by the global rush to contain the coronavirus pandemic that already has affected hundreds of thousands and killed more than 16,000 people worldwide, the Duke vaccine researchers are undeterred in their focus on the flu, a yearly scourge.
“The thing to remember is that while the new coronavirus is a current threat, influenza is a present and ongoing threat that has infected and killed more people this year,” said Michael Anthony “Tony” Moody, a pediatrician and immunologist who will lead Duke’s efforts to develop potential universal flu vaccines as part of the broader initiative. “[I]f anything, the current outbreak has highlighted all the work that remains to be done to protect us against these ever-emerging pathogens.”
If Moody and his team, or their cohorts around the globe, can find a way to lessen the flu’s impact, then future hospital beds would be freed up to allow doctors to combat other dangerous pathogens that the world has yet to see, or imagine.
Federal grants largest in Duke’s history
The universal flu vaccine grants awarded to Duke researchers by the National Institute of Allergy and Infectious Diseases (NIAID) this fall were the largest in Duke’s history for a single program.
The initial elation of being selected has worn off, as the reality of the challenge at hand set in.
“Now we’re kind of in the ‘be careful what you wish for’ phase,” Moody said. “It’s the ‘we got to get stuff done.’ But it’s the right problem to have.”
That’s because the threat of the flu isn’t going away unless researchers like Moody and his team rethink how to fight it.
Although vaccines for influenza already exist, they’re imperfect, with efficacy rates that range from 40 to 60 percent each year.
While the flu vaccine might not offer near-complete coverage, the way vaccines for diseases such as measles and polio can, the Duke University team strongly recommends people continue to seek out flu shots each year. The vaccines are proven to be safe and provide enough protection to reduce the duration and severity of disease even if a person contracts influenza, Moody said.
But the flu virus is a particularly vexing pathogen to combat because it’s always changing.
Each year’s flu vaccine is a scientific best guess at what might circulate during the upcoming season. Patients need to be vaccinated each season, which can be difficult to adhere to given changes in insurance, the demands of busy lives, and a lack of urgency for a virus that seems familiar. Then, of course, there are the battles doctors fight against the anti-vaccination movement’s attempts to undermine the science about the safety and necessity of vaccinations.
All those challenges result in just under 63 percent of children and 46 percent of American adults receiving influenza vaccinations last year, according to the CDC.
By looking instead at how an influenza vaccine should work against any and all strains of the flu, and not just an individual strain, would be of huge significance, said Emmanuel “Chip” Walter, a professor of pediatrics who serves as DHVI’s chief medical officer.
“You want to get a vaccine that protects against multiple flu strains and new flu strains that we haven’t even seen yet,” Walter said.
Why the pressure to fight flu is on
Just how to do that is the million-dollar question, or the $400 million question in Duke’s case.
The hunt for a universal flu vaccine remains a major focus for the federal government, backed with significant funding.
NIAID issued a challenge in 2018, calling on researchers to work toward the creation of a universal flu vaccine suitable for all age groups that could be at least 75 percent effective in protecting against two groups of the influenza A virus, with influenza B as a secondary target.
The NIAID awards went to four research universities, including Duke, which had past successes with ongoing work on HIV and AIDS vaccine development, and prompted the creation of the Collaborative Influenza Vaccine Innovation Centers (CIVICS) program, which aims to bring the best work of researchers together. The goal is to try and together accomplish what has previously escaped researchers: a working universal flu vaccine. Also selected for awards were the Icahn School of Medicine at Mount Sinai; the University of Georgia; and the University of Maryland’s School of Medicine.
Beginning with an initial injection of $29.6 million in first-year funding, the DVHI team at Duke were selected for three pieces of the research cycle: a vaccine development contract, vaccine manufacturing, and to fund clinical trials to test vaccine candidates coming out of Duke and the other institutes’ findings.
Duke was the only research center selected for all three components of the research cycle.
Researchers beyond those selected by NIAID are working on a universal flu vaccine as well, and one National Institutes of Health vaccine candidate went to an in-human clinical trial last year, an important step in the research agenda to observe how a vaccine performs in healthy adults.
How a universal vaccine may differ
Much of the research is focused on how the flu virus enters a cell to infect it. The flu virus, which originates in birds but has several strains that have infected humans, enters cells through a protein called hemagglutinin (HA). That HA protein consists of a head and a stem, according to the NIAID.
Current vaccinations work by inducing antibodies to target the head of the protein, which changes and morphs over the course of a season because of “antigenic drift” — the reason why creating an effective vaccine can be so elusive.
But the stem of the virus does not appear to change. So researchers at Duke and elsewhere want to figure out how to get antibodies to target that static stem to nullify a virus’ effects. Doing so could provide protection against whatever collection of flu strains emerge in a given year.
The researchers at Duke don’t expect to hit a bulls-eye the first time, or in the next year. They anticipate working closely with colleagues around the world to chip away at the answer, test it, and then circle back to look at what worked and what didn’t.
“Let’s come up with the best (vaccine) candidates, make them, put them into people, learn from it, and go back around,” Moody said. “That’s really what this whole program is about, to try to say, ‘Alright, what are the good ideas? Let’s test them.’”
How flu vaccine could change the tide
This year’s flu has been particularly dangerous for children, with the deaths of 149 children nationally attributed to the flu, the second-highest number of deaths since the CDC began tracking the information in 2004. North Carolina has seen 138 deaths this year, including four children.
Roz Fisher has learned a cruel lesson this year of how dangerous the flu can be. Her 15-year-old daughter Lacie Rian Fisher died of complications from the flu and septic shock in December. The Haywood County teenager’s death from the flu was something her mother never entertained as a possibility for a seemingly healthy teenager like Lacie, an active cheerleader.
“You don’t expect your loved one to die with a cold or the flu like that,” Fisher said. “You might get sick and feel like you’re dying, but not literally.”
The teen had gotten the flu vaccine in years past, but things slipped by and she didn’t get one for this year’s flu season.
It’s one of the hard “what ifs” Fisher has been left with, along with wondering what would have happened if Lacie had gone to a doctor sooner, or first gone to Mission Hospital, the Asheville-based hospital system, instead of the smaller Haywood Regional Medical Center.
Fisher knows examining the past won’t change her reality. But she hopes people hearing of her devastating loss will emphasize how important vaccinations are. The high school Lacie attended held a flu shot clinic shortly after the teenager’s death, and Roz Fisher hopes to see that continue.
The thought that there could one day be a universal vaccine where a child may only need one shot in a lifeline, or every few years, brings comfort to Fisher while she still grieves.
“If there could be any improvement, that would be a major step,” Fisher said.
And that’s the type of step Moody, Walters and their colleagues at the Duke Human Vaccine Institute are working on.
“It’d be great if we could get a home run,” Moody said. “We’re definitely open to that possibility.”