Discoveries in Airway Mucosal Immunology Herald New Strategies for Vaccine Development

Research program focused on preventing lethal viral infections

Medical illustration of nasal passages

The protective mechanisms in the nasal cavity that filter, humidify, and enrich inhaled air are well recognized and studied, but there is little research about the interactions between the nose and the lungs. A new research program in Duke’s Department of Head and Neck Surgery & Communication Sciences aims to further define these interactions and use the knowledge to explore new strategies for nasal vaccine development and disease prevention.

A top researcher in the field of airway mucosal immunology, Duke head and neck surgeon Xiaoyang Hua, MD, PhD, leads the program. He was the principal investigator for an exploratory study published in JCI Insight in July 2018 that led to a significant finding: the nose can effectively prime immunity to protect lungs against direct viral infections.

“The nose is a person’s first point of contact with the outside world,” says Hua, “and we know that it does a good job in minimizing detrimental physiological stimulation of the lower airway. But this is just physical protection, so our team wanted to explore the immunological interactions between the nose and lungs.”

The study involved delivering small volumes of a mild pneumotropic murine coronavirus intranasally in one group of mice, then delivering a lethal dose of an influenza virus directly into the lungs two days later. A second group of mice received the influenza virus only, without prior infection. Hua reports that the group of mice with a prior nasal infection had a 0% mortality rate, but the group without prior nasal infection had a 100% mortality rate.

The results are dramatic and encouraging, he says, because they indicate the nose and upper airway remotely prime both innate and adaptive immunity in the lungs to protect them from direct viral infections by recruiting activated monocytes (Ly6C+ inflammatory monocytes) and natural killer (NK) cells into the lungs. He adds that the findings may have important therapeutic implications for the use of nasal immunotherapy to prevent or reduce the severity of viral pneumonia, which currently causes significant morbidity and mortality and has limited treatment options.

Hua notes that the research involves an ongoing collaboration with Herman Staats, PhD, a Duke professor of pathology, whose expertise in mucosa vaccine development will guide researchers toward a better understanding of the factors that control the induction and regulation of mucosal immune responses.