Bacterial polysaccharide could lead to HIV vaccine.
The outer surfaces of human cells, bacterial cells and viruses often bear proteins that are glycosylated, that is, decorated with sugar molecules called polysaccharides. An unexpected similarity between the surface polysaccharides of human immunodeficiency virus (HIV) and a plant bacterium could point the way toward the world's first vaccine to prevent AIDS.
The surface of HIV has a glycosylated protein called gp120, which is heavily decorated with a type of polysaccharide called oligomannose. Although some humans can produce antibodies that bind the oligomannose sugar molecules, most cannot. This is because oligomannose sugars on HIV are so similar to the surface polysaccharides found on human cells that the immune system does not recognize them as foreign. The goal of HIV vaccine researchers is to find or create a polysaccharide that is different enough from the polysaccharides found on human cells to be recognized by the immune system, yet similar enough that the antibodies it generates will bind to oligomannose on HIV as well.
Ralph Pantophlet heads the Laboratory of Infectious Diseases Immunology in the Faculty of Health Science at Simon Fraser University, but his previous work involved studying surface polysaccharides in bacteria. Acting on a hunch, he emailed some of his former colleagues asking if they had seen any bacterial surface polysaccharides that resembled HIV-oligomannose. By sheer coincidence, a researcher in Italy named Cristina De Castro had recently isolated a new polysaccharide from a plant bacterium called Rhizobium rodiobocter. De Castro sent a sample to Pantophlet, who was surprised to discover that it was bound by a human antibody to oligomannose. "I thought we might find something that looked a bit like oligomannose on HIV, but that we would then need to chemically tweak it to make it more to our liking," says Pantophlet. "But to find a natural product that was so close was just amazing."
Pantophlet and his team have tried injecting heat-killed Rhizobium rodiobacter into mice to see if they generate oligomannose-specific antibodies. They did, but although these antibodies can bind to gp120, they weren't capable of blocking HIV from infecting cells in subsequent laboratory tests. Pantophlet hopes to improve the response by separating the polysaccharide from the bacterium and fixing it to another protein that can trigger the immune system to make better antibodies. If the new glycoprotein elicits the desired response, Pantophlet hopes that a prototype vaccine could be created in three to five years. The research is published in Chemistry and Biology.
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|Publication:||Canadian Chemical News|
|Date:||Apr 1, 2012|
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