Most vaccines and boosters are given as injections into muscle tissue, typically the upper arm, to activate the body’s immune system. However, for respiratory illnesses like COVID-19, protecting the respiratory tract—the primary entry point of the virus—is especially important.
A new study from Yale researchers reveals that nasal vaccine boosters can effectively stimulate strong immune defenses in the respiratory tract, even without the use of immune-stimulating additives called adjuvants. These findings, published in Nature Immunology, offer promising insights for the development of safer and more effective nasal vaccines.
“We found that a simple viral protein antigen delivered nasally can boost immune responses right where viruses enter the body,” said Akiko Iwasaki, Sterling Professor of Immunobiology at Yale School of Medicine and senior author of the study. “This suggests nasal sprays with viral proteins could safely enhance antiviral immunity at the site of infection.”
The study, led by postdoctoral fellow Dong-il Kwon, involved priming mice with a traditional intramuscular mRNA COVID-19 vaccine, followed by a nasal booster containing spike protein but no adjuvants—a strategy the team calls “prime and spike.” After the first shot, immune cells were primed in lymph nodes. The nasal booster then triggered B cells to migrate to the lungs and produce immunoglobulin A (IgA), an antibody that protects the nose and lungs from infection. Memory helper T cells supported this process by acting as natural adjuvants.
Importantly, only the nasal booster induced this strong local immune response. Boosters administered intramuscularly did not generate significant IgA or activate lung immune cells. A second nasal booster further increased IgA levels in the respiratory tract.
“Regular COVID-19 shots don’t induce much IgA in the nose and lungs, which means vaccinated people can still become infected or spread the virus,” explained Kwon. “Our findings clarify why nasal boosters don’t need adjuvants to stimulate mucosal immunity and can guide safer vaccine designs against respiratory viruses.”
Iwasaki added, “Understanding how a simple nasal booster promotes protective immunity in the respiratory tract will accelerate development of this approach for human use.”
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