Discovery of key protein's shape could lead to improved bacterial pneumon...( pneumoniae do not work in young childr...),Health

pneumoniae do not work in young children. Adult vaccines are composed of pieces of carbohydrates naturally appearing on the surface of these bacteria. When used in a vaccine, these pieces of carbohydrate stimulate the immune system to make antibodies against the real carbohydrate targets on the bacteria. The problem with such vaccines is that the immune systems of very young children (younger than two years) do not naturally respond to carbohydrates. Pneumococcus vaccines for children must instead be modified by binding those carbohydrates to special proteins that stimulate the immune systems of young children.

"However such vaccines are so complex that they can carry carbohydrate targets for only a few specific strains of pneumonia bacteria," Tuomanen said. "So children are always under-protected, since there are so many different strains of these bacteria."

Knowing the shape of CbpA will guide researchers in their efforts to use part or all of this protein as the basis of a vaccine against S. pneumoniae.

"CbpA is a very large protein," Tuomanen said. "Now that we know what it looks like and how it's put together, we can pull it apart to see if smaller pieces of it can be used to make a vaccine that triggers production of antibodies against the CbpA. Since all the S. pneumoniae strains need CbpA to invade the bloodstream, we can widen the protection of a vaccine to all 90 types of pneumococcus by just adding CbpA, or a piece of CbpA."

The discovery of the structure of CbpA was a two-step process that included studies of how this protein works, followed by determination of its actual structure using powerful laboratory tools.

Previous work by another team suggested that CbpA binds to pIgR. However, that finding was made in "test-tube" experiments without using actual bacteria. So the St. Jude team developed pneumococcus bacteria that had mutated CbpA in order to prove that live bacteria with mutated CbpA could not bind to pIgR on cell
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
21-Dec-2004

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