How protein structures help to build better vaccines
The method has been used to design a more effective vaccine for leptospirosis.
Vaccines encourage the immune system to develop a protection against disease-causing bacteria and viruses. Some types of immune cells release antibodies, which recognize particular proteins on the surface of the invading microbe. A vaccine that contains these surface proteins allows immune cells to develop the antibodies that can help to fight off an infection at a later date. Studying the shape and structure of the surface proteins can reveal how they are detected by our immune systems and can further be used to design more effective vaccines.
Leptospirosis is the most common bacterial disease to affect both humans and animals. The symptoms of the disease include fever, muscle pain and bleeding from the lungs. New vaccines against leptospirosis are desperately needed because current ones have severe side effects and do not fully protect against the disease. The most promising new vaccine candidates are the Lig proteins, which are found on the surface of leptospirosis causing bacteria cells, but little was known about their molecular structure.
The region of the Lig protein that is recognized by the immune system consists of a series of twelve connected ‘immunoglobulin-like’ domains. Hsieh, Ptak et al. used X-ray scattering to determine the structure of this region and found that the protein is highly elongated. Additional experiments showed that the individual domains provoke immune responses to different extents. Antibodies that can interact more strongly with the Lig protein were also better able to kill the bacteria. Based on this information, Hsieh, Ptak et al. combined parts of the individual domains that bind strongly to antibodies to design a new protein that, when used as a vaccine, protected hamsters against leptospirosis much better than other Lig protein-based vaccines.
Further engineering and testing are required to develop an optimized, commercial leptospirosis vaccine, but the work of Hsieh, Ptak et al. shows the effectiveness of structure-based vaccine design methods. In the future, similar methods could be used to develop better vaccines and treatments for other infectious diseases.
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