Experimental Vaccine Against E. coli O157

Scientists at the National Institute of Child Health and Human Development (NICHD) have developed an experimental vaccine against Escherichia coli O157, the pathogenic bacterium that causes severe food poisoning and that prompted the recall last year of millions of pounds of ground beef.

Food poisoning with E. coli O157 is particularly dangerous in the young, claiming the lives of four children in 1993 and leaving many others permanently injured, after they had eaten tainted hamburgers at a West-Coast fast food chain. The severe complications of this disease are hemorrhagic colitis (resulting in bloody diarrhea) and hemolytic uremic syndrome (damage to the kidneys, ultimately leading to kidney failure). Both of these complications can be fatal, especially in children. Although E. coli O157 causes disease in humans, the bacterium lives in cattle and other domesticated animals without causing symptoms. Contamination of meat during butchering is believed to be the primary source of the bacterium, although indirect contamination of fruits and vegetables by cattle feces has also been implicated. The disease can also be acquired by swimming in contaminated lakes or ponds.

The U.S. Centers for Disease Control and Prevention (CDC) estimates that 20,000 people are infected with E. coli O157 each year, and about 250 people die of the infection.

To make an effective vaccine, the NICHD scientists chemically linked (conjugated) a polysaccharide (sugar chain) from the capsule of the bacterium to the genetically inactivated toxin from another bacterium, Pseudomonas aeruginosa. Conjugation of polysaccharides to proteins makes them much more effective vaccines than the polysaccharide alone. Two of the NICHD scientists associated with the E. coli vaccine won the Lasker Award in 1996 for the successful application of this principle to eradicating Hemophilus influenzae type b, which causes meningitis in children.

In a clinical trial, the vaccine against E. coli O157 caused volunteers to produce enough antibody to kill the bacteria in laboratory cultures, without serious side-effects in the volunteers (a few of the vaccinees had a mild skin reaction at the injection site). The power of the vaccinees’ serum to kill the bacteria persisted throughout the clinical trial, which lasted for 6 months. The results of this clinical trial are reported in an article in the February issue of the Journal of Infectious Diseases. The NICHD scientists propose that this conjugate vaccine-induced bactericidal activity is a correlate of immunity.

Humans do not develop the ability to make antibodies against polysaccharides until the age of about two. In contrast, proteins are effective antigens at all ages, which is why conjugating polysaccharides to proteins is such an important advance in making vaccines. The immune system of vaccinees receiving the conjugate makes antibodies against the capsule as if it were a protein.

The deadly E. coli O157 is a new pathogen, which some scientists believe originated during a Shigella pandemic in Central America that occurred in the 1970s, when a bacterial virus transferred the gene for the Shiga toxin from Shigella to E. coli, the normally harmless inhabitant of our intestines. The ability to immunize against this disease is particularly important, because the infection does not respond well to antibiotics; indeed it is thought that they may, in fact, increase the incidence of hemolytic uremic syndrome by causing the bacteria to burst and release the Shiga-like toxin into the bloodstream.

Although further clinical trials are required before the vaccine is declared protective in humans, the scientists are considering another strategy to eradicate E. coli O157--mass vaccination of cattle--which would eliminate the pathogen at its major source.

Editor’s note: the sequence following the species name of the bacteria begins with a capital letter "o," and not with the numeral "0".