Many viruses and bacteria infect humans through mucosal surfaces, such as those in the lungs, gastrointestinal tract and reproductive tract. To help fight these pathogens, scientists are working on vaccines that can establish a front line of defense at mucosal surfaces.

Vaccines can be delivered to the lungs via an aerosol spray, but the lungs often clear away the vaccine before it can provoke an immune response. To overcome that, MIT engineers have developed a new type of nanoparticle that protects the vaccine long enough to generate a strong immune response — not only in the lungs, but also in mucosal surfaces far from the vaccination site, such as the gastrointestinal and reproductive tracts.

Such vaccines could help protect against influenza and other respiratory viruses, or prevent sexually transmitted diseases such as HIV, herpes simplex virus and human papilloma virus, says Darrell Irvine, an MIT professor of materials science and engineering and biological engineering and the leader of the research team. He is also exploring use of the particles to deliver cancer vaccines.

Only a handful of mucosal vaccines have been approved for human use; the best-known example is the Sabin polio vaccine, which is given orally and absorbed in the digestive tract. There is also a flu vaccine delivered by nasal spray, and mucosal vaccines against cholera, rotavirus and typhoid fever. 

To create better ways of delivering such vaccines, Irvine and his colleagues built upon a nanoparticle they developed two years ago. The protein fragments that make up the vaccine are encased in a sphere made of several layers of lipids that are chemically “stapled” to one another, making the particles more durable inside the body.

This allows the particles to resist disintegration once they reach the lungs. With this sturdier packaging, the protein vaccine remains in the lungs long enough for immune cells lining the surface of the lungs to grab them and deliver them to T cells. Activating T cells is a critical step for the immune system to form a memory of the vaccine particles so it will be primed to respond again during an infection.

Mice vaccinated with nanoparticles were able to quickly contain the virus and prevent it from escaping the lungs. Vaccinia virus usually spreads to the ovaries soon after infection, but the researchers found that the vaccinia virus in the ovaries of mice vaccinated with nanoparticles was undetectable, while substantial viral concentrations were found in mice that received other forms of the vaccine.

Mice that received the nanoparticle vaccine lost a small amount of weight after infection but then fully recovered, whereas the viral challenge was 100 percent lethal to mice who received the non-nanoparticle vaccine.

The researchers also found a strong memory T cell presence at distant mucosal surfaces, including in the digestive and reproductive tracts. “An important caveat is that although immunity at distant mucus membranes following vaccination at one mucosal surface has been seen in humans as well, it’s still being worked out whether the patterns seen in mice are fully reproduced in humans,” Irvine says. “It might be that it’s a different mucosal surface that gets stimulated from the lungs or from oral delivery in humans.”

A researcher says the nanoparticles are “an exciting and effective strategy for inducing effector-memory T-cell responses to nonreplicating subunit vaccines through mucosal vaccination.”

“More research will need to be conducted to determine the delivery approach to be used in humans, but this vaccination strategy is particularly important for diseases that may require significant T cell-mediated protection, such as HIV,” says Herbst-Kralovetz, who was not part of the research team.

This story is reprinted from material from MIT, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.