Testing New TB Vaccines

Tuberculosis is the world’s deadliest infectious disease, sickening eight million people and killing two million every year. A century-old vaccine prevents childhood forms of the disease. But there’s a desperate need for a vaccine that’s effective against the adult form of the disease, which is highly contagious and is growing resistant to drug treatment. Renewing hope on this front, two human trials of vaccines that could be protective against the adult form of the disease began in the United States earlier this year.

In one of the trials, Corixa, a biotech firm in Seattle, WA, and GlaxoSmithKline Biologicals of Rixensart, Belgium, are testing the safety of their vaccine on 20 healthy volunteers. Whereas the childhood vaccine consists of live bacteria closely related to the TB-causing germ, the new one is made of two proteins isolated from the TB bacterium using genetic-engineering techniques. Corixa researchers picked these proteins in part by screening the blood of adults who successfully fought off the infection. Because their immune cells-presumably adept at killing tuberculosis germs-most readily recognized these two proteins, it’s thought that the proteins will stimulate a stronger and more effective immune response among adults. And because it’s not live, the vaccine could be easier to manufacture and store in large quantities, says Christine Sizemore, tuberculosis program officer for the National Institute of Allergy and Infectious Diseases in Bethesda, MD.

A second U.S. clinical trial, led by Marcus Horwitz, a professor of medicine and microbiology at the University of California, Los Angeles, is using a live vaccine in which the same organism used in the childhood vaccine has been engineered to produce extra immune-stimulating proteins. Even if these trials go well, it could be another decade before a new tuberculosis vaccine gets regulatory approval, says Sizemore. But after years of lackluster progress against the killer disease, even getting this far is, in her words, “a true quantum leap.”

Others Battling TB
Researcher	Technology
Stewart Cole Pasteur Institute, Paris, France	Same TB bacterium relative used in existing vaccine, but engineered to carry several genes from the TB bacterium; in animal testing
Helen McShane University of Oxford, Oxford, England	Genetically engineered virus carries a protein from the TB bacterium; in early human trials in the U.K. and the Gambia
Fordham von Reyn Dartmouth Medical School, Hanover, NH	Heat-killed bacteria related to the tuberculosis bacterium; in human trials with HIV-positive subjects in Tanzania