Vaccines work by exposing the body to an infectious agent in order to prime the immune system to respond quickly when it encounters the pathogen again. Some vaccines, such as the diphtheria vaccine, consist of a synthetic version of a protein or other molecule normally made by the pathogen, while others, such as the polio and smallpox vaccines, use a dead or disabled form of the virus. However, such an approach cannot be used with HIV because it's difficult to render the virus harmless. MIT engineers have now developed a new type of nanoparticle that could safely and effectively deliver vaccines for infectious diseases such as HIV and malaria, and could even help scientists develop vaccines against cancer.
When designing a vaccine, scientists either try to provoke T cells, which attack body cells that have been infected with a pathogen, or B cells, which secrete antibodies that target viruses or bacteria present in the blood and other bodily fluids. However, for diseases such as HIV in which the pathogen tends to stay inside cells, a strong response from a type of T cell known as a "killer " T cell is required.
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The best way to provoke these killer T cells into action is to use a killed or disabled virus, but the difficulty in rendering HIV harmless and the danger of using live viruses has led to scientists working on synthetic vaccines for HIV and other viral infections, such as hepatitis B. However, while these synthetic vaccines are safer, they do not elicit a very strong T cell response.
Recently, scientists have tried encasing the vaccines in fatty droplets called liposomes, which could help promote T cell responses by packaging the protein in a virus-like particle. However, these liposomes have poor stability in blood and body fluids and tend to break down quickly inside the body.
Darrell Irvine, an associate professor of materials science and engineering and biological engineering at MIT, decided to build on the liposome approach by packaging many of the droplets together in concentric spheres. Once the liposomes are fused together, adjacent liposome walls are chemically "stapled" to each other, making the structure more stable and less likely to break down too quickly following injection. However, once the nanoparticles are absorbed by a cell, they degrade quickly, releasing the vaccine and provoking a T cell response.
In tests with mice, Irvine and his colleagues used the nanoparticles to deliver an egg-white protein called ovalbumin. This protein is commonly used in immunology studies because there are biochemical tools available to track the immune response to this molecule. They found that three immunizations of low doses of the vaccine produced a strong T cell response with up to 30 percent of all the killer T cells in the mice specific to the vaccine protein after immunization.
Irvine is now working on developing the nanoparticles to deliver cancer and HIV vaccines, while additional studies are examining their potential for delivering a malaria vaccine. The new nanoparticles developed at MIT are described in the Feb. 20 issue of Nature Materials.View gallery - 2 images