Vaccine confers pertussis protection.

Vaccine confers pertussis protection

An international scientific team reports this week that two forms of a genetically engineered vaccine protect mice from whooping cough, a respiratory infection caused by the bacterium Bordetella pertussis. That report may represent a significant step toward a safer pertussis vaccine for humans.

Whooping cough - which gets its name from the "whoop" sound victims make as they inhale after a bout of violent coughing - annually affects an estimated 60 million people and kills one million people worldwide. An effective vaccine, made from killed B. pertussis cells has been available in the United States since the 1940s. But that vaccine commonly causes minor side effects and in rare cases causes brain damage and even death. Concern over the safety of the whole-cell vaccine has led to the development of so-called acellular pertussis vaccines, made by chemically inactivating a purified pertussis toxin. But those vaccines, now in U.S. clinical trials, can also cause side effects because the chemical treatment sometimes allows some pertussis toxin to regain its toxic activity.

Rino Rappuoli of the Sclavo Research Center in Siena, Italy, Joseph T. Barbieri of the Medical College of Wisconsin in Milwaukee and colleagues took a different approach. They altered the gene that codes for the pertussis toxin, a protein produced by B. pertussis. When inserted into a strain of B. pertussis, the altered gene led to the production of new toxins lacking the amino acids that cause toxicity. Yet these mutant toxins still triggered an immune response in mice, they report in the Oct. 27 SCIENCE.

The scientists used the altered toxins to make two experimental vaccines. They gave mice varying doses of both vaccines and challenged them 15 days later with an injection of virulent B. pertussis. Two weeks after the challenge, the mice showed 100 percent survival at vaccine doses causing no serious side effects.

Rappuoli and colleagues suggest their genetically engineered vaccine avoids the problems of previous vaccines because they've produced a permanently harmless pertussis toxin.

Rappuoli started testing the genetically engineered vaccine in 20 Italian volunteers aged 25 to 35 this week. If that pilot study indicates the vaccine is safe, Rappuoli plans to ask the Food and Drug Administration for approval to test the vaccine in a U.S. clinical trial by the end of 1989.