Mar. 16, 1999 Autoimmunity, in which the body attacks its own tissues, has traditionally been viewed as spelling nothing but trouble. But now Weizmann Institute scientists have shown that it's possible to "enlist" an autoimmune mechanism for a beneficial cause -- fighting outside intruders such as bacteria. This new approach may lead to the development of improved vaccines for preventing various infectious diseases and possibly for treating cancerous tumors.
The emergence of drug-resistant bacteria and the growing concern over the appearance of intractable infections have recently brought new urgency to the search for improved vaccines. A vaccine's job is to trigger the production of antibodies against an infectious agent. Ideally, the antibodies should be high-performance, that is, quick to appear, long-lasting and capable of improving themselves with time. Such antibodies can only be created if they are produced with the assistance of the immune system's T-helper cells, which provide their help once they spot the infectious agent. Unfortunately, many infectious organisms camouflage themselves in a sugary coat so that the T cells can't see them. In such cases, the antibodies that are produced are of lower quality and less effective fighters against disease.
To outwit the camouflaged bacteria, scientists have begun to resort to a sophisticated approach: when designing improved vaccines, they attach vaccine molecules to "carrier" proteins that stimulate T cells and enlist them in the antibody production process. However, until now these carrier proteins have had a major drawback: in most cases, they came from diphtheria and tetanus bacteria and, as a result, they tended to trigger the production of antibodies against themselves, a process which interferes with the creation of the antibodies needed to prevent the disease.
This is where the Weizmann Institute's new concept comes in. Prof. Irun Cohen of the Immunology Department had the clever idea of replacing the diphtheria- and tetanus-derived carriers with heat-shock proteins, so called because they are produced by the body in response to stress situations. People are born with a natural immunity to these proteins, which are known to stimulate T-helper cells.
"Heat-shock proteins are perfect enhancers of the T-helper cell response,but because they are part of autoimmunity -- the body's reaction against its own components -- no one thought of redirecting their activity to fight an external threat such as infection," Cohen says. He conducted the study, reported in February in the Journal of Infectious Diseases, with Prof. Mati Fridkin and with Drs. Stephanie Konen-Waisman and Avi Cohen.
The scientists immunized mice with a vaccine composed of a heat-shock protein carrier attached to the sugar-coat molecule of a dangerous pneumococcal bacterium. The immunized mice were then infected with lethal doses of the bacteria. Ordinarily, 2-3 bacteria of this type suffice to kill an unprotected mouse within a day or two. In the study, the heat-shock-protein vaccine offered nearly complete protection against a bacterial army of several million. This protection was a thousand times greater than that provided by a commercial pneumococcal vaccine, which only succeeded in partially fighting off an infection of 1,000 pneumococcal bacteria.
The Weizmann team now plans to test the effectiveness of the new approach -- patented through Yeda Research and Development Co., the Institute's technology transfer arm -- for vaccinations against tuberculosis and viral infections. The scientists are also considering a vaccine for use in cancer therapy, in which the immune system would be activated to attack tumor cells, thus preventing their spread.
Prof. Cohen holds the Helen and Morris Mauerberger Chair in Immunology and heads both the Weizmann's Robert Koch Minerva Center for Research in Autoimmune Diseases and the Center for the Study of Emerging Diseases in Jerusalem. Prof. Fridkin holds the Lester B. Pearson Chair of Protein Research. The study was partially funded by Peptor Ltd. and a Center of Excellence grant from the Israel Science Foundation.
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