Can an Immunotherapy Based on Smallpox Vaccine Reverse Lung Fibrosis? New Study Yields Surprising Results

Johns Hopkins School of Medicine researchers demonstrated that the smallpox vaccine may reverse established lung fibrosis in mice. The vaccine changed the reactivity of various types of immune T-cells, suggesting that balancing the actions of these immune players could be crucial in developing immunotherapeutic treatments for lung fibrosis.

Scientists have known for some time that immune T-cells play a role in the development of fibrosis, but it has not been clear what factors make the cells promote a fibrotic response. Recently, a particular type of tissue-resident memory T-cells was discovered. These cells are crucial to the quick launch of immune responses when a pathogen that previously caused infection is encountered, and to interacting with other immune system cells to unleash an array of inflammatory factors.

Researchers used a mouse model of lung fibrosis induced by the drug bleomycin, to which they administered the smallpox vaccine intranasally and analyzed the mice lungs after an additional period. Findings, published in the journal JCI Insight, showed that the mice receiving the vaccine had less inflammation and less collagen in their lungs. The study is titled “Vaccinia vaccine-based immunotherapy arrests and reverses established pulmonary fibrosis.”

Administering the vaccine at different time points, letting some mice develop severe fibrosis, was found both to halt the development of further fibrosis and, in fact, reverse the fibrotic process in severely affected mice — a potentially huge advance on current treatments able only to slow disease progression. The mice also had lower levels of fibrocytes, a cell type found in peripheral blood associated with fibrosis formation. The study also showed that the lung function of the mice improved after receiving the vaccine.

Analysis of cell and molecular changes in the lungs showed an increase in one type of T-cell, releasing the protective factor IFN-g, while other types of T-cells that release inflammation-promoting IL-17 were found in lower numbers. Regulatory T-cells — a type of cell also associated with the resolution of inflammatory responses — were unaffected by the vaccine.

Further analyses revealed that the vaccine triggered the development of a specific type of tissue resident memory T-cell. Blocking the development of this type of cell while leaving other T-cell types intact prevented the beneficial effects of the treatment.

The authors concluded that an immunotherapeutic approach based on vaccination and directed to the lungs could be explored as a treatment for pulmonary fibrosis, and that targeting tissue-resident memory T-cells might be a promising strategy to treat tissue-specific inflammatory/autoimmune disorders.