Could A Nasal Vaccine Finally Get Rid Of The Black Death?

December 02, 1998

NOSE drops can protect mice from bubonic plague, the disease that wiped out a third of Europe's population in the 14th century. If this new vaccine also works in human trials, it may allay fears of a worldwide pandemic started by antibiotic-resistant plague bacteria.

Round the world, one to two thousand cases of the plague are reported each year. Bubonic plague is caused by the bacterium Yersinia pestis, which is spread by fleas that live on rodents. But the bacteria can also spread directly into the lungs through infected droplets coughed out by sick people. This pneumonic plague spreads faster and is more deadly than the bubonic form, and was the main cause of the Black Death.

Antibiotics can save someone with pneumonic plague if they get treatment within 18 hours of infection. But last year, researchers found plague bacteria in Madagascar carrying five different antibiotic resistance genes. This raised the spectre of a pneumonic plague pandemic. The disease could also become a weapon in the hands of bioterrorists.

Many researchers pin their hopes on an effective vaccine. The only vaccine now licensed for plague, which consists of killed bacteria, protects just half its recipients. Clinical trials of a vaccine that may be more effective will start next year. "But that vaccine must be injected, which presents logistical problems if you have to give it quickly to 100 000 soldiers or civilians," says Rick Titball of Britain's Defence Evaluation Research Agency in Porton Down, Wiltshire. Ideally, he adds, the vaccine should be in a form that can target tissue lining the gut or respiratory system.

That is what Oya Alpar and her colleagues at the University of Birmingham have come up with. They took a protein from the surface of Y. pestis and combined it with another that is secreted by the bacterium. They encapsulated the proteins in polylactic acid polymers to stop them being broken down by enzymes in the body before reaching their target.

The researchers say mice whose noses and throats were treated with the vaccine were fully protected from inhaled Y. pestis (Vaccine, vol 16, p 2000). Tests showed that the capsules released the proteins for several weeks, and the mice produced two types of antibodies: one secreted by the tissue lining the gut and respiratory system, and another which circulates in the blood.

Alpar says a nasal spray based on this vaccine could be a viable means of protecting people from pneumonic plague, and she is planning clinical trials. "We think this is a promising approach for a whole range of diseases," she adds. "We are looking at similar vaccines for tetanus and diphtheria."
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