Nasal vaccine shows promise in boosting lung immunity against flu

A new experimental nasal vaccine has demonstrated the ability to restore some of the diminished immune function in aging lungs and provided laboratory mice with strong protection against various influenza strains, opening the door to more effective respiratory vaccines for older adults.

Researchers said a single dose of the vaccine, which uses a novel immune-boosting adjuvant called AMnESTI, triggered immune responses in older mice that approached those seen in younger animals.

Many vaccines become less effective with age due to multiple changes in the immune system, including increased inhibitory signals and weaker type I interferon responses in the lungs, making older adults more vulnerable to severe complications from flu and other respiratory infections.

The team developed the new adjuvant as lipid vesicles that mimic natural lung components and specifically target alveolar epithelial cells, which line the tiny air sacs where oxygen exchange occurs.

These vesicles carry manganese ions along with a substance that activates the innate immune pathway known as cGAS-STING, helping the body detect threats and launch an early immune response.

Experiments published in the journal Science Advances showed that nasal delivery of the adjuvant activated this pathway in lung cells, increased numbers of certain immune cells—including dendritic and inflammatory monocyte cells—and at the same time reduced the immune suppression associated with aging.

Single-cell RNA analysis revealed that the treatment reshaped the immune environment in the lungs of older mice, making their responses more similar to those of younger animals.

When the researchers added the adjuvant to a flu vaccine, a single dose was enough to stimulate a strong CD8 T cell response and provided broad protection against several different flu strains.

The researchers noted that these findings could be significant because current flu vaccines are less effective in some older adults, who are among the groups most at risk of severe illness and death during flu seasons or pandemics.

However, the study was conducted in mice, and the results do not yet prove the vaccine can restore immunity or prevent flu in humans. Further studies are needed to assess the vaccine's safety and effectiveness before clinical use.

The researchers suggested testing the new adjuvant in future studies with other vaccines targeting respiratory diseases that could cause large-scale outbreaks.