BOTULISM VACCINE CREATED AT UCSF 



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Last Updated

06 Nov 2002

Source: The Mercury News (San Jose), August 5, 2002.

Botulism vaccine created at UCSF

Drug shows promise as defense against bioterrorism strike

Mercury News

Bay Area scientists have created the first drug that could be cheaply mass-produced to treat botulism, the paralyzing disease caused by a potent toxin on America's short list of bioterrorism threats.

The drug, composed of manufactured antibodies, has been tested only in mice but could be publicly available in two to four years, said Dr. James Marks, a University of California-San Francisco antibody expert who led the Department of Defense-funded project. The drug is effective against a form of the toxin considered most likely to be used in a bioterrorist attack -- the same form used, in low doses, in the popular wrinkle-smoother Botox, Marks said.

Botulinum toxin, produced by a soil bacterium, can shut down breathing within hours. It is considered the single most poisonous substance in the world. A single gram of the toxin, if properly distributed, could kill a million people. Iraq has produced botulinum toxin, as did the United States and the Soviet Union before a 1972 treaty outlawing biological and chemical warfare.

An easily produced anti-botulism drug could save many lives in the event of a terrorist attack, researchers say; the UC-San Francisco drug works quickly and can protect people for up to six months. The drug neutralizes the toxin by binding to it and disabling it.

The UC-San Francisco findings, the result of eight years of research, are being published online this week by the Proceedings of the National Academy of Sciences.

"We've known this was a possibility,'' said Frances Edwards-Winslow, director of emergency preparedness for the city of San Jose. ``It's really very encouraging to see how far along they are.''

The research also carries significance beyond botulism, according to researchers in the field who say it could pave the way for new avenues of drug development.

Disease rare in U.S.

Naturally occurring botulism, which can result from wound infections, soil contact or contaminated food, is rare in the United States. Infants have sometimes contracted it from eating honey or accidentally ingesting or inhaling soil particles. Adults may be struck after eating improperly canned food or injecting contaminated heroin. About 110 cases of botulism are reported to the U.S. Centers for Disease Control and Prevention (CDC) each year.

The toxin prevents nerve endings from sending signals to muscles, leading to paralysis. Some victims require a ventilator for six weeks or more, leading bioterrorism experts to worry that even a small-scale attack could overwhelm a community's medical resources.

Although some bioweapons experts believe botulism is less of a threat than smallpox or anthrax because it as not as easily "weaponized'' -- the toxin cannot survive for long in air or treated water supplies -- it remains on the CDC's list of most likely bioweapons.

An experimental vaccine exists, but it is given primarily to laboratory workers who may come into contact with the botulinum toxin. Mass vaccinations, even if a safe vaccine were approved, would not be a good idea because the vaccine would prevent people from receiving the botulism toxin for Botox injections or, more importantly, therapies that use parts of the toxins to ease migraine headaches, relieve muscle spasms and treat head injuries, Marks said.

Antibiotics like Cipro don't work against botulism: Although they kill bacteria, they are ineffective against the toxin it produces. Antitoxins are available, but they are in scarce supply and are closely held by public health departments.

Current antitoxins, derived from horses, also carry side effects and are too difficult to produce in large amounts. A safer antitoxin researched by the California Department of Health Services and designed for babies is awaiting federal approval. But it too cannot be produced in sufficient quantity, said Dr. Robert Schechter, clinical director of the department's Infant Botulism Program.

Marks and his team had long sought -- in vain -- a single antibody to combat the powerful botulinum toxin. In the end, they combined three "monoclonal antibodies'' -- identical antibodies produced by cultured cells -- that bind to different parts of the toxin's protein molecule to disable it.

The means for producing such antibodies is already in commercial use and could be scaled to create large quantities of the drug, Marks said. The drug could also be stockpiled because of the long shelf life of human antibodies. First, however, UC-San Francisco researchers must find a commercial or government partner to help develop the drug by steering it through a series of clinical trials toward federal approval.

Further applications

Schechter, of the California Department of Health Services, said the UC-San Francisco research shows promise for treating not just botulism, but also other toxins and infections: Although there are numerous monoclonal drugs in development, this is the first to show that three different antibodies can be successfully incorporated into one drug.

"Dr. Marks and his team have shown that a combination of antibodies is greater than the sum of their parts. It's closer to the full immune response that humans and animals make,'' Schechter said. "There are many exciting aspects to this work.''