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Mizzou researchers link poor sleep to weaker immune responses and reduced vaccine effectiveness
By Sophie Rentschler | MU Division of Research
Poor sleep’s consequences may ripple far beyond feeling tired in the morning; it could also weaken how well vaccines protect you.
In a new study, University of Missouri researchers found that chronically fragmented sleep (CSF) reduces both the strength and quality of immune responses, potentially limiting the effectiveness of influenza vaccination.
“Many people today struggle to get consistent, high-quality sleep,” said Xiu-Feng (Henry) Wan, senior author and director of the NextGen Center for Influenza and Emerging Infectious Diseases at Mizzou. “Our findings suggest that sleep is an important factor that may influence how well vaccines work.”
The researchers analyzed clinical data from more than 900,000 adults who received the seasonal flu vaccine. Individuals with obstructive sleep apnea — a condition characterized by constantly waking up for short periods of time and failing to enter a state of deep sleep — showed a significantly higher risk of flu infection after vaccination.
To understand why, the team turned to controlled experiments in mice.
Using nocturnal mice that typically sleep during the day, the scientists kept the lights on and used a device that woke up the mice whenever they began to doze off by slowly advancing a metal bar startle them. This disturbance mirrors sleep troubles for those with severe obstructive sleep apnea.
Animals exposed to sleep disruption produced significantly fewer antibodies following vaccination compared to well-rested mice.
Collaborator Alex Gileles-Hillel of Hebrew University emphasized the strength of combining this human and animal data.
“By analyzing both animal models and human data, we were able to show that inadequate sleep severely curtails the body’s proper immune response to the seasonal flu,” Gileles-Hillel said.
At the cellular level, the scientists examined what these differences meant.
“What surprised us most was how broadly the immune system was affected,” said Minhui Guan, who conducted the work as a Mizzou postdoctoral researcher and is now a research scientist in Wan’s lab and first author of the study. “It wasn’t just a reduction in antibodies — we saw coordinated changes in multiple immune cell types, suggesting sleep disruption fundamentally reshapes how the immune system responds to vaccination.”
By using single-cell RNA sequencing, researchers measured changes in genes.
They noticed that genes for B cells — white blood cells responsible for producing antibodies — were disrupted in sleep-deprived mice, reprogramming how these cells produce antibodies. The findings help explain how disrupted sleep weakens immune protection.
The changes didn’t stop at B cells. Sleep disruption also altered how the B cells interact with T cells — immune cells that help coordinate immune responses — in ways that may further compromise effective immune function.
David Gozal, dean of Marshall University’s Joan C. Edwards School of Medicine, who co-conceptualized the study with Wan, highlighted the clinical implications.
“When sleep is disrupted, the body’s ability to mount a strong immune response to vaccination is compromised,” Gozal said.
Poor sleep is widespread, and CSF affects about one-third of the global population. The study describes fragmented sleep as repeated disturbances that prevent the body from reaching deep, restorative sleep. You could liken it to sleeping on an airplane but being disturbed by the air pressure, the guy snoring in the seat next to you or the stewardess making announcements.
Some populations particularly vulnerable to fragmented sleep are shift workers, parents of young children, frequent travelers, and health care workers.
When it comes to the flu, the Centers for Disease Control and Prevention estimates that in 2023, 14 million people visited a doctor, 360,000 were hospitalized and 21,000 died. It wrote that flu vaccines can reduce the risk of doctor visits by 40-60 percent.
Gileles-Hillel said the project is a “wonderful example of interdisciplinary research.”
“By bringing together the unique expertise of sleep researchers, immunologists, and virologists, we can connect the dots across different fields and make important discoveries that have a real-world impact on public health,” he said.
The researchers are now studying whether the immune effects of disrupted sleep can be reversed after recovery.
The study was published in April 2026 in Nature Communications.
Wan is a Curators’ Distinguished Professor at the University of Missouri School of Medicine and the Colleges of Veterinary Medicine and Engineering. He’s also a principal investigator at the Bond Life Sciences Center and director of the NextGen Center for Influenza and Emerging Infectious Diseases.
In addition to Wan and Guan, Mizzou study authors also include Weihong Gu, Pradeep Balamalaliyage, Wikanda Tunterak, Moran Li, Yi Huang, Yuhan Wen, and John Driver, PhD. This research was a collaborative effort involving Marshall University (Abdelnaby Khalyfa and David Gozal); Hebrew University (Alex Gileles-Hillel). The study was supported by the University of Missouri.
