Influenza kills more than 35,000 people in the U.S. each year, and vaccination remains the best defense—but current vaccines don't always stop the virus from taking hold in the respiratory tract in the first place. New research suggests a previously overlooked group of immune cells in the lungs may help close that gap.
Rethinking immune memory
After an infection or vaccination, the immune system forms “memory” cells that can respond quickly if a virus returns. In the lungs, these T-cells serve as a first line of defense right where viruses enter the body.
However, most current flu vaccines do not reliably build strong immune memory in the airways, leaving a gap in protection against initial infection and transmission.
In their study, published in Nature Immunology, researchers found that a subset of monocytes can persist in the lungs for months after influenza infection. Rather than disappearing, these cells appear to support immune memory by helping tissue-resident memory T-cells survive and function.
“Our work identified a long-lived monocyte-derived population in the lung that provides essential support for durable T-cell immunity,” said Minsoo Kim, professor of microbiology and immunology at the University of Rochester Medical Center and lead author of the study. “This challenges the traditional view that immune memory is driven only by T- and -B cells, and shows that innate immune cells also play a lasting role.”
Rethinking nasal vaccines
The team also identified how these monocyte-derived cells communicate with T-cells: they produce a protein called galectin-1, which helps activate and sustain the memory T-cells.
When the researchers added galectin-1 to an experimental nasal flu vaccine in mice, the immune response in the lungs grew significantly stronger.
“This is a completely new approach for improving how vaccines work in the respiratory tract,” said Kim.
Existing nasal vaccines often fail to generate strong or durable protection. This study suggests that enhancing interactions between innate immune cells and memory T-cells could be key.
Rethinking infection and disease
The researchers say the findings may extend beyond influenza to other respiratory viruses that cause seasonal illness and pandemics.
“We now see that innate immune cells are not just first responders—they can also shape long-term immune memory,” Kim said. “This opens up the possibility of designing vaccines that intentionally reprogram these cells to improve protection.”
The team is now developing more stable forms of galectin-1 that could be safely used as a vaccine additive. If the findings translate to humans, they could shift how respiratory vaccines are designed—moving beyond antibody responses and circulating immune cells to also target the long-term behavior of immune cells that live in the lungs themselves.
The team hopes the work could eventually lead to vaccines that not only prevent severe disease, but stop infection earlier, at the point where it starts.