University of Tokyo Study Shows Nasal Adjuvant Protects Mice from Flu for 100 Days

Researchers at the University of Tokyo have developed a nasal vaccine additive that provides mice with broad protection against influenza for over 100 days after a single dose. The study, published October 9 in Science Advances, identifies a specific nanoparticle combination that effectively “trains” the immune system in the lungs to repel respiratory threats without requiring a specific match to a virus strain.

The research, led by Professor Ken Ishii of the Institute of Medical Science at the University of Tokyo, centers on a nasal adjuvant known as K3-SPG. This substance is a nanoparticle that combines synthetic DNA (CpG) with schizophyllan, a sugar derived from fungi. When administered through the nose, the adjuvant does not just assist a vaccine in creating antibodies; it fundamentally alters how the lung’s local immune cells respond to invaders.

Trained immunity in alveolar macrophages provides a first line of defense against respiratory pathogens.

The 100-Day Protection Gap

A primary challenge in pandemic preparedness is the time required to develop, manufacture, and distribute a new vaccine once a novel virus emerges. This window, often referred to as the “100-day gap,” leaves populations vulnerable. The K3-SPG adjuvant is designed to serve as a pathogen-agnostic shield during this period. Because it stimulates a general immune response rather than a virus-specific one, it can theoretically offer broad protection against respiratory viruses that have not yet been identified.

In the study, mice treated with the nasal additive showed significantly higher survival rates when exposed to Influenza A, even when the exposure occurred more than three months after the initial treatment. This duration is notable because innate immune responses—the body’s first line of defense—typically dissipate within days or weeks.

Trained Immunity in the Lungs

The long-lasting nature of the protection is attributed to a biological process called “trained immunity.” The researchers found that the K3-SPG adjuvant induces epigenetic changes in alveolar macrophages, which are specialized immune cells residing in the lung tissue.

By “reprogramming” these macrophages, the adjuvant ensures the cells remain in a heightened state of readiness. When a virus enters the respiratory system, these trained cells respond more aggressively than they would under normal conditions. This localized approach specifically targets the site of infection for most respiratory pathogens, preventing the virus from establishing a foothold in the deep lung tissue.

While the study was conducted on mouse models, the findings align with global initiatives like the “100-Day Mission”—a goal backed by the G7 and the Coalition for Epidemic Preparedness Innovations (CEPI) to have interventions ready within three months of a pandemic threat. The University of Tokyo team suggests that a nasal spray utilizing this “pathogen-agnostic” approach could eventually provide a critical first line of defense for humans while specific vaccines are still in production.

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