Research at MIT suggests that an inhaled vaccine may trigger a strong immune response against infections and even cancer in the lungs. The findings could be good news for people at risk for the rare lung-related cancer, pleural mesothelioma.
Lung infections often start on mucosal membranes. So researchers developed a vaccine that binds to a protein in mucus. When they immunized mice in a way that mimics an inhaled vaccine, their lungs produced many T-cells. T-cells are immune system cells that can help fight infections and cancer.
Pleural mesothelioma is caused by exposure to asbestos. Right now, there is no way to vaccinate against it and no cure. If an inhaled vaccine could bring more T-cells to the lungs of at-risk people, it might help prevent mesothelioma tumors.
The Advantage of an Inhaled Vaccine
In their new paper, the MIT scientists focused on triggering an immune response. The immune system is a powerful ally against cancers like malignant mesothelioma. If a T-cell recognizes a cancer cell as an enemy, it can kill it before the cell turns into a tumor.
An inhaled vaccine is of special interest to doctors who treat patients with lung conditions like pleural mesothelioma or lung cancer. Unlike vaccines that go into a muscle, an inhaled vaccine goes directly into the lungs.
Pleural mesothelioma occurs on the membrane around the lungs. It can spread into the lung tissue and, eventually, into other organs, too. The key to preventing the spread of mesothelioma and many other kinds of cancer is to stop it before it develops.
MIT researchers theorized that if an inhaled vaccine could bring more T-cells to the mucosal membrane, these immune system cells might have a better chance to kill potential cancer cells.
Crossing the Mucosal Barrier
The MIT researchers published their findings in the journal Science Immunology. Lead researcher Darrell Irvine says his team used the protein albumin as a sort of “Trojan horse” to get the test vaccine across the mucosal barrier.
“In some cases, vaccines given in muscle can elicit immunity at mucosal surfaces, but there is a general principle that if you vaccinate through the mucosal surface, you tend to elicit a stronger protection at that site,” Irvine said in an MIT article on the new research.
That is exactly what happened with the simulated inhaled vaccine. Dr. Irvine and his team created a peptide vaccine against the vaccinia virus. They gave the vaccine a “tail” that binds to the protein albumin.
Then they gave the vaccine to one group of mice as a muscle injection. Other mice got the vaccine directly in their trachea, which simulates inhalation. The mice that got the inhaled vaccine had a 25-fold increase in memory T-cells in their lungs.
They tried a similar strategy with a vaccine against melanoma. When immunized mice were exposed to melanoma cells, T-cells in the lungs eliminated them. The same strategy might one day be used to deliver a vaccine against malignant pleural mesothelioma.
Only a small number of asbestos-exposed people develop mesothelioma. But once a person is exposed to asbestos, there is no way to prevent the disease. Exposed people should know the symptoms of mesothelioma and get regular checkups. About 2,500 Americans receive a mesothelioma diagnosis every year.
Rakhra, K, et al, “Exploiting albumin as a mucosal vaccine chaperone for robust generation of lung-resident memory T cells”, March 19, 2021, Science Immunology, https://immunology.sciencemag.org/content/6/57/eabd8003