Cholera Vaccine Developed

Bacteria that cause cholera can get their deadly poison from a virus infection, Medical School researchers have discovered.

The invading virus carries genes necessary to turn even a harmless bacterium into a killer.

"This dumb bacterium doesn't know how to cause disease, and the virus instructs it by introducing the cholera gene into its genome," says John Mekalanos, Higgins Professor of Microbiology and Molecular Genetics.

The finding is part of a research effort that also has led to development of a vaccine for the two most lethal strains of cholera, known as the Bengal and El Tor strains.

"It should be possible to immunize people against all forms of cholera with vaccines based on these two strains," Mekalanos believes.

He and Matthew Waldor, now at the New England Medical Center in Boston, worked out the story of how the two organisms cooperate to produce cholera. Bacteria, clinging to the lower parts of the intestinal walls send out slender receptors called pili. The virus attaches itself to these bristles, slips inside the bacterium and deposits its package of genes. The viral toxin gene then is activated by the same gene that activated the bristling pili. This clever strategy enables the virus to bring toxin only to bacteria located in a place and state where they can trigger the disease.

"The virus says to the bacteria, 'You have to bring something to the party - the pili - but I'll bring the band and we'll have a dance,' " Mekalanos comments.

The couple interacts with the cells of the intestines to trigger diarrhea so devastating it can kill unless a victim is treated promptly with antibiotics.

Mekalanos and his colleague devised a vaccine that prevents the bacteria from getting to the dance hall where the action occurs. Their vaccine contains toxin-free bacteria made so large that they can't swim down the lower levels of the intestinal walls where they take root. The body's immune system spots the stalled cells and kills them. The strategy should work on both El Tor and Bengal strains.
The next step would be to vaccinate volunteers caught in natural epidemics, such as those that have ravaged India, South America, and Africa in the 1990s. In 1991, more than 500,000 people fell ill in South America and close to 500 died from cholera.

To produce large supplies of it, Harvard has patented the vaccine and licensed it to a biotechnology company.
- William J. Cromie