Johns Hopkins researchers believe they’ve figured out how to fix a popular nasal spray vaccine that federal authorities told people to stop using last year because it offered little protection from the flu.
That would be welcome news for needle-averse children and adults who dread getting a shot even if it protects them against the respiratory virus that infects millions of Americans every year and can be dangerous for the elderly, chronically ill and very young.
The researchers at Johns Hopkins Bloomberg School of Public Health discovered a previously overlooked mutation in one of the influenza strains used to build the spray vaccine that could be altered to make it work better, according to a paper published recently in the journal Vaccine.
“There isn’t a good explanation of why the vaccine has been failing, but this gives us a path forward,” said Andrew S. Pekosz, professor in the Bloomberg School’s department of molecular microbiology and immunology. “It’s exciting because the vaccine has been an important tool for a number of years, particularly in children.”
When the U.S. Centers for Disease Control and Prevention recommended against using the FluMist vaccine last season, it was a stunning reversal for the nation’s only nasal spray, used widely since it was approved in 2003 for those aged 2 to 49.
Researchers across the country and at Gaithersburg-based MedImmune LLC, which makes FluMist, have been scrambling to figure out why the spray vaccine’s effectiveness in preventing flu appeared to diminish in recent years.
A spokeswoman for MedImmune’s parent company, AstraZeneca, the giant Swedish pharmaceutical firm, said they were aware of the Hopkins researchers’ findings and “look forward to reviewing the research.”
The company, meanwhile, also has identified “multiple potential root causes and potential contributing factors” for the vaccine’s reduced effectiveness, said Abigail Bozarth, the AstraZeneca spokeswoman. Company officials hope to have more information from a study later this year, she said.
It could take some time to prove the Hopkins method works and is safe for humans, and MedImmune may figure out how to fix FluMist another way before then, but the progress gave advocates of vaccination hope for eventually getting another option to help people stave off the nasty virus.
“Being able to offer mist and injectable vaccine could be appealing to parents,” said Tiffany Tate, executive director of the nonprofit Maryland Partnership for Prevention. “I would like to always offer both.”
Tate’s nonprofit worked with five school systems in the state this year to vaccinate students. The shots were tolerated well by even the youngest children, she said, but, if the spray returned, more school systems might offer the vaccine and more parents might be willing to let their children get vaccinated.
The shots not only can induce tears in children but take about 50 percent more time to administer and require more supplies, such as alcohol swabs, bandages and disposal containers, Tate said. The spray requires little more than tissues and sanitizer.
She estimates about 47,000 were vaccinated in Maryland schools this year by her group or directly by school systems. That was up from last year, when the spray first became unavailable, but down from the highs of about 100,000 students vaccinated when the systems used the spray.
The Hopkins researchers led by Pekosz, whose lab investigates viruses including the ones that cause influenza, discovered the potential fix accidentally.
The lab was investigating something else when Pekosz’ team found the mutation in the H1N1 strain of influenza and realized they could tweak it to change the strain’s behavior and possibly restore the power of FluMist.
H1N1 is one of the permanent strains used to make the spray vaccine, which depends on live but weakened viruses rather than the dead ones used in injectable vaccines. Other strains in the vaccine change each year to match those expected to be circulating during the season.
The mutation had slowed the strain’s activity so it wasn’t making enough copies of itself — a process known as replicating — to induce an immune response. When there is just enough replication, the immune system kicks in to ward off the virus without making the host sick.
Pekosz said he could increase replication in the strain and possibly others, even customizing it to various strengths necessary to protect different age groups — making it stronger for healthy adults and weaker for vulnerable individuals like small children.
While a modified vaccine based on the Hopkins research would take time to develop and prove safe, it wouldn’t face the same rigorous testing as a new vaccine, potentially shaving years off the approval process.
Despite the recommendations against FluMist, Tate and others still urge people to get a flu shot ahead of the holidays when travel and gatherings easily spread germs.
The CDC warned that this season could be a bad one given the level of infection in the southern hemisphere. Flu vaccines here are developed annually based on strains circulating there.
The Maryland Department of Health reported the state’s first flu case in October. Based on data from some doctors’ offices and hospitals, the health department said there have been 455 doctor visits for influenza-like illness and nearly 4,000 emergency room visits so far this season, which lasts roughly from October to May.
Experts say it’s tough to get an accurate count of flu cases because many people do not seek care, but ride out the fever, coughing and aches at home. As a result, most people aren’t lab tested for the flu.
“Influenza activity is not considered high at this time, but this fall we have seen localized outbreaks and hospitalizations associated with the influenza virus,” said Brittany Fowler, a spokeswoman for the health department. “The vaccine is widely available, and Maryland residents are urged to get protected now by scheduling an appointment with their health care provider, local health department or neighborhood pharmacy for vaccination.”
At Greater Baltimore Medical Center there have been few flu cases so far, said Dr. Jeffrey Sternlicht, who, as chairman of the emergency medicine department, has seen the misery of the flu and its strain on the hospital when cases outpace caregivers.
The hospital, like others in the region, has resorted to triaging patients in parking lot tents to handle large loads and to avoid spread of disease. A normal season brings in about 150 flu patients a day; a bad one brings in about 250, Sternlicht said. A vaccine is the best defense for anyone 6 months or older.
“I’ve gotten the flu shot every year since 1992,” he said. “I got the flu and said I never wanted it again. I felt awful, couldn’t get out of bed. … More importantly, I’ve seen plenty of people die. They are usually chronically ill and elderly, but young people can die. One of biggest mistakes for people is not getting the vaccine.”
The absence of spray doesn’t seem to have affected vaccination rates. The CDC reported that about the same proportion of American children, close to 60 percent, got a flu shot last year when there was no FluMist — basically unchanged from the year before, when the spray was still available.
That’s no surprise, said Dr. Adam Spanier, a pediatrician at the University of Maryland Medical Center. Parents who want their children vaccinated would not be dissuaded by the way it’s administered, he said.
Still, the spray would be welcomed back by parents who would endure less resistance from their children.
“If you gave the kids a choice, I’m sure they would prefer a nasal spray,” said Spanier, also an associate professor of pediatrics at the University of Maryland School of Medicine. “And happy patients makes me happy.”