Scientists at MIT have developed concentric fatty sphere nanoparticles that can deliver synthetically produced proteins typically manufactured by viruses. These packaged units activate a strong response from the immune system, but the researchers claim that this is a safer option than traditional vaccines because actual inactivated pathogens are not involved. Walter Reed Army Institute of Research has partnered with the MIT team to evaluate these nanopackages in laboratory mice.
For diseases in which the pathogen tends to stay inside cells, such as HIV, a strong response from a type of T cell known as “killer” T cell is required. The best way to provoke these cells into action is to use a killed or disabled virus, but that cannot be done with HIV because it’s difficult to render the virus harmless.
To get around the danger of using live viruses, scientists are working on synthetic vaccines for HIV and other viral infections such as hepatitis B. However, these vaccines, while safer, 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.
Irvine, who is a member of MIT’s David H. Koch Institute for Integrative Cancer Research, 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 a protein called ovalbumin, an egg-white protein commonly used in immunology studies because biochemical tools are 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 — after immunization, up to 30 percent of all killer T cells in the mice were specific to the vaccine protein.
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Abstract in Nature Materials: Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses
