THURSDAY, Nov. 14, 2002 (HealthDayNews) -- A vaccine to protect against sepsis, a potentially life-threatening disease that's on the rise in the United States, has performed well in animal studies.
That's the encouraging news from scientists at the Scripps Research Institute in La Jolla, Calif., who report their findings in the current issue of the international edition of the journal Angewandte Chemie.
Sepsis, also known as septic shock and systemic inflammatory response syndrome, is a severe illness caused by overwhelming infection of the bloodstream by toxin-producing bacteria. "It occurs in two of every 100 hospital admissions, and is caused by bacterial infection that can originate anywhere in the body," according to the National Institutes of Health.
It begins with an infection. The immune system is then activated and that sets off a cascade of events, such as uncontrolled inflammation and activation of the blood coagulation system. Next, there can be multiple organ failures, from which many sepsis patients eventually die.
Doctors have been successful at reducing the percentage of people who die from sepsis, which is generally treated with antibiotics to quell the infection. However, overall deaths are up as the incidence of sepsis has more than quadrupled in the United States in the past two decades.
In the past, other researchers have tried to protect against sepsis by infusing antibodies to target endotoxins. These are dangerous chemical components of certain bacteria that can cause the immune system to overreact and release lethal amounts of inflammatory chemicals, such as tumor necrosis factor alpha, or TNF-alpha. However, the results haven't been encouraging.
The new Scripps vaccine takes a more active approach. It aims to neutralize the endotoxins and prevent the overreaction of the immune system. The researchers vaccinated mice after giving them a sub-lethal dose of lipid A, a component of endotoxins, says Paul Wentworth Jr., an associate professor of chemistry at Scripps and a co-author of the study.
The vaccine produced a nearly 95 percent reduction in the production of TNF-alpha, a good indication that the vaccine controlled the body's response to infection.
"Normally the body makes TNF-alpha," Wentworth says. However, in the case of sepsis, its production can spiral out of control. "The TNF-alpha is a marker for the body's over-response to the bacterial endotoxins," he says.
"We think the vaccine is working in two ways," Wentworth adds. "It is binding to the lipid A and neutralizing its activity. And it could also be generating antibodies that catalyze the destruction of lipid A molecules."
Wentworth says the study, while promising, is preliminary. If continuing studies show positive results, he says the researchers hope that human trials could begin in the next five years or so. It would likely take a decade before the vaccine is on the market, he says.
Another expert calls the Scripps research and approach interesting.
"This [vaccine] is targeted to the reaction [by the immune system to the bacteria]," says Dr. Phil Dellinger, director of critical care medicine at Cooper Health System in Camden, N.J., and an expert on sepsis. One downside, he says, is that it would not work for "gram-positive infections," which he says are now more common causes of sepsis.
Wentworth says the Scripps team is working on a vaccine that would work against gram-positive infections as well.
What To Do
For more information on sepsis, visit the National Library of Medicine or this Eli Lilly and Co. site.
