H1N1 influenza virus particles

Getting Personal: The Future of Flu Vaccines

Does a 250-pound male linebacker need the same flu vaccine as a 120-pound female dancer? Probably not.

Biomedical research has established that factors such as gender, age and body composition can affect the body’s immune responses prompted by vaccination. Pregnancy, a weakened immune system, and allergies to substances like egg or yeast proteins in vaccines can also affect how the body reacts.

“Personalized” vaccines—shots tweaked to trigger the most effective immune response for specific populations—are a strategy that could have tremendous implications for curbing influenza and other disease outbreaks.

Nicholas Wohlgemuth, a PhD candidate in Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health, and colleagues recently made a discovery that could be an important step toward personalized vaccines. Wohlgemuth and his team have been tinkering with the live attenuated influenza vaccine (LAIV), which relies on a weakened (attenuated) virus to stimulate an immune response. Though licensed, this particular vaccine is not presently recommended in the U.S. because of its low effectiveness. This made it an excellent candidate for potential improvement.

In a recently published article in the journal Vaccine, Wohlgemuth et al. reported on their investigation into a mutation that weakens the virus in LAIV. While the mutations that weaken LAIV were identified several years ago, Wohlgemuth and his colleagues thought the previous work had limitations and might have missed some important mutations. The researchers zeroed in on a mutation in the virus’s M2 protein and found that altering the mutation can increase or decrease how quickly the virus replicates.

The team’s findings suggest that reversing the M2 mutation increases the virulence and could induce a more robust immune response in healthy people. It’s not yet clear if a counter measure could help reduce the vaccine’s potency to make it safer for immunocompromised patients. Regardless, manipulating mutations presents an obvious opportunity for “personalizing” vaccines—although a custom shot is still likely decades away.

Vaccines for viruses that evolve rapidly, like the flu, don’t provide lifelong immunity, but they do “give the immune system a head start, preventing illness and still inducing a robust, protective immune response,” Wohlgemuth says. For viruses such as Ebola, SARS and HIV, which replicate so quickly that they can skirt a host’s immune response, it’s not known what attenuation levels would make for a safe vaccine—and that’s before considering age, body type, gender and other factors. It’s unlikely that a standard-dose vaccine could work for any of these viruses, making them prime candidates for mutation experimentation. “Going forward,” Wohlgemuth says of these viruses, “we should consider multiple attenuation strategies from the beginning since we know that one size may not fit all.”

Justin Ortiz, MD, an associate professor at University of Maryland’s Center for Vaccine Development, notes that understanding why vaccines like those for influenza seem to work better for some groups than others is key to developing the next generation of vaccines. “[Wohlgemuth’s] study identifies interesting possibilities for altering replication of LAIVs in ways that could be important to tailor vaccine characteristics based on the needs of target groups,” Ortiz says.

If a future pandemic on the scale of the 1918 flu occurs, halting or even curbing infection rates will require different vaccination strategies. Yet while viruses are rapidly mutating away, vaccine development crawls along a timeline defined by painstaking clinical trials, funding demands and lengthy vaccine production schedules.

“Given a hypothetical, deadly pandemic, it would be short-sighted and potentially dangerous not to consider testing the vaccine in a variety of populations or even developing multiple vaccines concurrently in order to better protect the population as a whole,” Wohlgemuth says.


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H1N1 influenza virus particles shown in a colorized transmission electron micrograph. (Image: NIH/Wikimedia Commons)