Disease bugs come equipped with a whole tool kit of tricks for evading our immune system. Now it seems that turning off just one of them can render bubonic plague harmless. A similar approach might lead to vaccines against many pathogens, including antibiotic-resistant hospital superbugs.
When you recover from an infection, antibodies produced by your long-term immune cells often prevent you catching the same disease again. What enables you to survive that initial infection is 鈥渋nnate鈥� immunity, a fiendishly complicated network of chemicals that recognise foreign invaders, unleash immediate defences against them and marshal long-term immunity.
Yersinia pestis, the bacterium that causes bubonic plague, possesses at least four mechanisms for evading our innate immune system. These include a switch that turns off the normal cell-surface molecules that strongly stimulate the innate immune system when plague gets into the body
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Egil Lien and colleagues at the University of Massachusetts in Worcester created a strain of Yersinia that couldn鈥檛 make this one switch, leaving the other three mechanisms intact. To their amazement, they found that the bacterium was so disabled that the mice didn鈥檛 get sick, even when given very high doses of it.
If the mice were treated so they couldn鈥檛 make antibodies to the modified Yersinia, they still died 鈥� but nine days later. 鈥淭he innate immunity keeps the mouse alive while it makes its long-term immunity. In the end, it needs both,鈥� Lien says.
Crucially, the mice injected with the modified bacteria made effective antibodies that later completely protected them against normal plague.
鈥淲e are investigating whether this could be used as a vaccine,鈥� says Lien. He hopes similar modifications might also lead to vaccines against relatives of plague, such as chlamydia, which causes urinary and reproductive tract infection, and tularemia, which, like bubonic plague, is considered a potential bioweapon. Many of the most important antibiotic-resistant bacteria are also relatives of plague.
