Luring the bacteria into an evolutionary trap

Using the technology researchers have developed a vaccine that protects animals from Salmonella bacteria

July 7, 2021
The Scitech

Researchers at ETH Zurich and the University of Basel have developed a vaccine that protects animals from Salmonella. These bacteria often escape the effects of vaccination by genetically modifying their protective coat. The researchers have succeeded in manipulating this process to lure the bacteria into an evolutionary trap. Developing vaccines against bacteria is in many cases much more difficult than vaccines against viruses. Like virtually all pathogens, bacteria are able to sidestep a vaccine’s effectiveness by modifying their genes. For many pathogens, such genetic adaptations under selective pressure from vaccination will cause their virulence or fitness to decrease. This lets the pathogens escape the effects of vaccination, but at the price of becoming less transmissible or causing less damage. Some pathogens, however, including many bacteria, are extremely good at changing in ways that allow them to escape the effects of vaccination while remaining highly infectious.

For scientists looking to develop vaccines, this kind of immune evasion has been a fundamental problem for decades. If they set out to develop vaccines against bacterial pathogens, often they will notice that these quickly become ineffective. Now, however, researchers at ETH Zurich and the University of Basel have exploited precisely this mechanism to come up with an effective vaccine against bacteria. They succeeded in developing a Salmonella vaccine that, instead of trying to outright kill intestinal bacteria, rather guides their evolution in the gut to make them a weaker pathogen. “This allowed us to show that immune evasion is not only a major challenge in vaccine development, but that it can in fact be put to good use in both human and veterinary medicine,” explains ETH Professor Emma Slack.  In their study, the researchers inoculated mice with a series of slightly different vaccines against Salmonella typhimurium, and observed how the Salmonella in the animals’ guts modified their genes to escape the vaccines’ effects. This let the scientists identify the full spectrum of possible immune evasion mutations in Salmonella typhimurium. Subsequently, the researchers produced a combination vaccine from four Salmonella strains that covered the bacteria’s full spectrum of genetic evasion options. A surprising immune evasion was driven by this combined vaccine, causing an important Salmonella sugar coating on the surface to atrophy. While the affected bacteria were still able to multiply in the animals’ guts, they were largely unable to infect body tissues and cause disease.

Source: ETH Zurich news release