A Shockingly Versatile Vaccine

For vaccines to teach the body to recognize a pathogen, they must insert a diagnostic fragment into macrophages and other cells of the immune system. Viruses can do the job, but they can be dangerous--especially in patients whose immune systems are already compromised by a viral infection. Now, researchers report that a simple bacterial protein can act as a carrier, priming the immune system to react to specific foreign proteins. The new technology, reported in the current issue of the Proceedings of the National Academy of Sciences, might be adaptable into a delivery system for AIDS vaccines.

The key to the new technology is a protein called hsp70, which belongs to a group of proteins known as "heat shock proteins" or "stress proteins" found in bacteria and higher organisms. These proteins strongly stimulate the mammalian immune system. Over the past few years, several research groups have created vaccines that protect mice against cancer by injecting them with stress proteins isolated from the mouse's own tumor cells. Now, immunologist Rick Young and his colleagues at the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology have coaxed a mouse's immune system to recognize other proteins by attaching them to heat shock proteins isolated from tuberculosis bacilli and injecting the combination into the animal.

The group created a prototype mouse vaccine by linking a protein called chicken ovalbumin to the tuberculosis protein hsp70. Then they implanted into the mice a genetically engineered line of cancer cells festooned with ovalbumin protein. Normally, these cancer cells would overwhelm the host's immune system. But because hsp70 somehow made the target known to the immune systems of the host mice, the ovalbumin on the cancer cell surfaces was like a bull's-eye in the sights of a sharpshooter. The mice's immune systems responded enthusiastically, killing the invading cancer cells. After 40 days, 80% of the protected mice were still alive, while all of the control mice had died of tumors.

Heat shock proteins are "much safer" than viral vaccines, says Michael Starnbach, an immunologist at Harvard Medical School in Boston. And even though researchers don't know how heat shock proteins sneak into killer T cells, they might be able to deliver just about any antigen. "That's exciting," says Starnbach.