University of Rochester Medical Center researchers have identified a previously overlooked group of immune cells in the lungs that may help explain how the body builds lasting protection against influenza — and could eventually lead to more effective nasal flu vaccines.
The study, published in Nature Immunology, found that certain monocyte-derived immune cells can remain in the lungs for months after a flu infection and help sustain tissue-resident memory T cells, which serve as a first line of defense where respiratory viruses enter the body.
Researchers also identified a protein called galectin-1 as an important part of that process. When galectin-1 was added to an experimental nasal flu vaccine in mice, the immune response in the lungs became significantly stronger.
Minsoo Kim, a professor of microbiology and immunology at UR Medicine and lead author of the study, said the findings challenge the traditional view that long-term immune memory is driven mainly by T cells and B cells.
The research suggests innate immune cells — usually thought of as short-term responders — may also have an important role in maintaining protection long after an infection has passed.
That could matter for future flu vaccines because current vaccines do not always produce strong immune memory in the respiratory tract.
Most flu vaccines are injected into muscle and are effective at reducing the risk of severe illness, but they do not consistently prevent infection from becoming established in the nose and lungs. Nasal vaccines are designed to target that problem, but their effectiveness has been inconsistent.
Kim said tissue-resident memory T cells are especially important because they are already positioned in the lungs and airways when a virus arrives.
“These cells are positioned right where infection begins, so they can react immediately and help limit viral spread,” Kim said.
The new research focused on how those cells are created and maintained.
Researchers found that a subset of monocytes remained in the lungs far longer than expected after influenza infection. Instead of disappearing, the cells appeared to support memory T cells and help them survive and function over time.
The team then identified galectin-1 as one of the signals those monocyte-derived cells use to communicate with T cells.
When researchers added the protein to an experimental nasal vaccine in mice, it produced a stronger immune response in the lungs, raising the possibility that galectin-1 could eventually be used as a vaccine adjuvant — an ingredient intended to enhance the body’s immune response.
“This is a completely new approach for improving how vaccines work in the respiratory tract,” Kim said.
The findings are still preliminary. The experiments were conducted in mice, not people, and researchers said more work is needed before galectin-1 could be considered for use in human vaccines.
The UR Medicine team is now working on developing more stable forms of the protein that could potentially be used safely as a vaccine additive.
The implications may also extend beyond influenza.
If the same immune mechanisms operate in humans, future vaccines against other respiratory viruses could be designed to build stronger and more durable protection directly in the lungs rather than relying primarily on antibodies or circulating immune cells elsewhere in the body.
That could create a different goal for vaccination: not only preventing severe disease after infection occurs, but improving the body’s ability to stop or contain infection earlier at the point of entry.
For now, the research represents an early-stage finding rather than a new vaccine option. But it gives scientists a new target to investigate as they work toward more durable protection against influenza and other respiratory illnesses.
The study included researchers from UR Medicine and the Korea Research Institute of Chemical Technology. Funding came from UR Medicine, the National Institute of Allergy and Infectious Diseases, the National Heart, Lung, and Blood Institute, the National Research Foundation of Korea and the Korea Research Institute of Chemical Technology.
FingerLakes1.com is the region’s leading all-digital news publication. The company was founded in 1998 and has been keeping residents informed for more than two decades. Have a lead? Send it to news@fingerlakes1.com.