A new flu vaccine approach using immune cell-derived vesicles could significantly improve protection against evolving influenza viruses, researchers say.
A Flu Shot That Might Finally Keep Up With the Virus
ATLANTA—A new study out of Georgia State University is shaking up how scientists think about flu vaccines. Researchers found that using immune cell-derived vesicles—tiny packages secreted by mature dendritic cells—as a nasal spray adjuvant makes flu vaccines much more effective. In tests on mice, the team saw broader immune protection and stronger defense against different strains of influenza.
That’s a big deal in a world where seasonal flu shots often miss the mark. Existing vaccines are updated each year based on forecasts of circulating strains, but sometimes those guesses fall short. This new research hints at a way to make flu vaccines more adaptable and potent—especially in how they activate the immune system at mucosal surfaces, like inside the nose.
The Science Behind the Spray
The study, published in ACS Nano, focused on a type of protein-based vaccine that targets hemagglutinin, a key protein on the surface of the flu virus. These subunit vaccines are considered safer and cheaper to produce—but they’ve always had one major drawback: they don’t trigger strong immune responses unless combined with an effective booster or adjuvant.
That’s where the immune vesicles come in.
In this case, researchers extracted extracellular vesicles from mature bone marrow-derived dendritic cells. These cells are like frontline messengers for the immune system, responsible for activating T cells and shaping immune responses. According to Dr. Bao-Zhong Wang, senior author and Distinguished University Professor at Georgia State, the vesicles from these mature dendritic cells pack a powerful punch.
Why Mucosal Immunity Matters More Than You Think
Most flu vaccines are injected into the muscle, triggering a systemic immune response. But flu is a respiratory virus—it enters through the nose and throat. That’s why mucosal immunity, the kind that defends the body at entry points like the respiratory tract, is so important. It’s the first barrier.
Dr. Wang’s team wanted to see if nasal delivery could kickstart a better line of defense.
And it did. Mice given the hemagglutinin vaccine along with the vesicle-based adjuvant had more active B cells, more macrophages, and more immune activity in airway tissue.
Here’s what researchers observed:
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Strong activation of antigen-presenting cells
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Boosted lymphocyte response in the lungs
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Better formation of “germinal centers,” which are critical for producing high-quality antibodies
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Evidence of cross protection against flu strains that weren’t in the original vaccine
Study Details: What They Did and What They Found
The research used both in vitro (lab-based) and in vivo (animal-based) methods to test the effect of vesicle adjuvants.
They compared the results of vesicles from immature versus mature dendritic cells. Only the mature ones showed meaningful immune activation.
To simplify their findings:
| Immune Marker | With Mature Vesicles | Without Vesicles |
|---|---|---|
| B Cell Activation | High | Low |
| Antigen Presentation | Strong | Weak |
| Germinal Center Size | Large | Minimal |
| Cross Protection | Observed | Not Observed |
These results support a clear conclusion: not all adjuvants are created equal, and using immune-system-derived vesicles might be a smarter route.
What Makes These Vesicles So Special?
Extracellular vesicles aren’t new to science. They’ve been studied for years for their role in cell-to-cell communication. But using them as vaccine enhancers? That’s newer territory.
And what makes these vesicles particularly useful, according to Wang, is their natural design. “They’re already built by the immune system,” he said. “They know how to talk to other cells.”
That natural compatibility likely explains why the immune system responded so well. Instead of fighting off a synthetic chemical booster, the body recognizes and accepts the vesicles—and gets to work.
Big Promise, But Still Early Days
The findings are exciting, but they’re still limited to preclinical stages. The tests were done in mice, not humans. Clinical trials would be the next logical step, and those could take years.
Still, researchers are hopeful. The potential here isn’t just about flu—it’s about developing mucosal vaccines for other respiratory diseases. COVID-19, RSV, and even tuberculosis could benefit from the same science, if it holds up in further testing.
Emma Robinson, a junior geoscience major at Georgia Southern who wasn’t involved in this study but has worked on field-based health surveys in Bangladesh, said, “It’s this kind of research that gives you hope. It’s smart, and it’s rooted in how nature already works.”
The Urgency of a Better Flu Vaccine
Why now? Because the flu virus keeps changing. The World Health Organization estimates that seasonal flu kills between 290,000 and 650,000 people globally every year. While mRNA vaccines and AI-based forecasting have helped, there’s still a huge gap in protection—especially when it comes to mutating or mismatched strains.
Current vaccine efficacy can dip as low as 10% in some seasons, which isn’t good enough for high-risk populations.
Dr. Wang believes this vesicle strategy could push that number way higher.
“It’s not about re-inventing the immune system,” he said. “It’s about working with it.”
What Happens Next?
More animal trials, then human safety studies. Researchers say they’re looking to collaborate with pharmaceutical partners to move things along. But for now, it’s still a lab success story—one with real-world potential.
If it works, the idea of a nasal flu spray that actually gives strong, cross-strain immunity might finally become more than a hope.
