New research led by Penn State scientists, published on March 13 in the journal Science Advances, reports that targeting two specific proteins on the surface of the influenza virus could help reduce its airborne transmission without increasing viral evolution inside hosts.
The findings are significant because they address a longstanding question in vaccine design: whether vaccines should focus on stopping virus replication within an infected individual or preventing the spread to others. The study suggests that both goals can be achieved simultaneously by focusing immune responses on hemagglutinin (HA) and neuraminidase (NA), two key influenza proteins.
"This suggests that intentionally targeting these two proteins together in future vaccines could help curb spread," said Troy Sutton, who led the study and serves as Huck Early Career Chair in Virology and associate professor of immunology and infectious disease at Penn State. "Critically, transmission was reduced without accelerating viral evolution inside the host, which is a key concern in vaccine design."
The researchers used ferrets as animal models to test how immunity from vaccination or prior infection against an H1N1 influenza strain affected both viral replication and airborne transmission. Sutton said, "The virus used in our study is considered representative of seasonal influenza viruses, or viruses that cause outbreaks every fall and winter." Ferrets were chosen because their respiratory systems closely mimic those of humans when it comes to infection and transmission of influenza viruses like H1N1.
The team found that animals with immunity to both HA and NA were consistently less likely to transmit the virus to uninfected ferrets. Transmission rates dropped by half when both proteins were targeted. Sutton described this effect as additive rather than synergistic, meaning each protein contributed equally to reducing transmission risk. The researchers also identified a threshold below which early viral levels resulted in less than a 50% chance of spreading the virus.
Importantly, no evidence was found that targeting both HA and NA drove rapid viral adaptation or emergence of escape variants among dozens of animal models tested. "Our work strengthens the growing consensus among experts that influenza vaccines need to target multiple influenza virus proteins to be maximally effective," Sutton said. He added that future vaccines may need not only strong antibody responses but also strategies to blunt spread at its source by doubling up on immune targets.
