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Sep 26, 2013

Nanoparticles Show Promise for Vaccine Delivery to Lungs

  • Researchers at MIT say they have developed a novel type of nanoparticle that protects a vaccine long enough to generate a strong immune response both in the lungs and in mucosal surfaces far from the vaccination site, such as the gastrointestinal and reproductive tracts.

    The scientists are working on this project since many viruses and bacteria infect humans through such mucosal surfaces and because the lungs often clear away a vaccine before it can stimulate an immune response.

    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, notes Darrell Irvine, Ph.D., 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.

    Dr. Irvine and colleagues, working with mice, describe the nanoparticle vaccine (“Generation of Effector Memory T Cell-Based Mucosal and Systemic Immunity with Pulmonary Nanoparticle Vaccination”) in the September 25 issue of Science Translational Medicine.

    “Nanocapsules primed 13-fold more T cells than did equivalent soluble vaccines, elicited increased expression of mucosal homing integrin α4β7+, and generated long-lived T cells in both the lungs and distal (for example, vaginal) mucosa strongly biased toward an effector memory (TEM) phenotype,” wrote the MIT team. “These TEM responses were highly protective in both therapeutic tumor and prophylactic viral vaccine settings.”

    Dr. Irvine and his associates 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.

    In studies of mice, the researchers found that HIV or cancer antigens encapsulated in nanoparticles were taken up by immune cells much more successfully than vaccine delivered to the lungs or under the skin without being trapped in nanoparticles.

    HIV does not infect mice, so to test the immune response generated by the vaccines, the researchers infected the mice with a version of the vaccinia virus that was engineered to produce the HIV protein delivered by the vaccine.

    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.

    Mice that received the nanoparticle vaccine lost a small amount of weight after infection but then fully recovered, whereas the viral challenge was 100% 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.



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