Attract bacteria into a trap
Developing vaccines against bacteria is in many cases much more difficult than vaccines against viruses. Like virtually all pathogens, bacteria are able to bypass the effectiveness of a vaccine by altering their genes. For many pathogens, such genetic adaptations under the selective pressure of vaccination will result in a decrease in their virulence or fitness. This allows pathogens to escape the effects of vaccination, but at the cost of becoming less transmissible or causing less damage. However, some pathogens, including many bacteria, are extremely effective at changing so as to escape the effects of vaccination while remaining highly infectious.
For scientists looking to develop vaccines, this type of immune breakout has been a fundamental problem for decades. If they set out to develop vaccines against bacterial pathogens, they will often notice that these quickly become ineffective.
Arming the immune evasion
Today, however, researchers at ETH Zurich and the University of Basel have exploited precisely this mechanism to develop an effective vaccine against the bacteria. They succeeded in developing a vaccine against salmonella which, instead of trying to outright kill gut bacteria, instead guides their evolution in the gut to make it a weaker pathogen.
“This has enabled 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 human and veterinary medicine,” explains the professor at the ‘ETH Emma Slack. “We can use it to drive the evolution of pathogenic microorganisms in a certain direction – in our case, a dead end.” Slack led the study, which involved many researchers from different groups at ETH Zurich and other institutions, as well as ETH professor Wolf-Dietrich Hardt and Médéric Diard, professor at the University’s Biozentrum. from Basel.
Combination vaccine leads to goal
In their study, the researchers inoculated mice with a series of slightly different vaccines against Salmonella typhimurium and observed how Salmonella in the intestines of the animals altered their genes to escape the effects of the vaccines. This allowed scientists to identify the full spectrum of possible immune breakout mutations in Salmonella typhimurium. Subsequently, the researchers produced a combined vaccine from four strains of Salmonella that covered the full spectrum of the bacteria’s genetic escape options.
A surprising immune breakout was caused by this combination vaccine, causing a large layer of Salmonella sugar to atrophy on the surface. While the affected bacteria were still able to multiply in the intestines of animals, they were largely unable to infect body tissue and cause disease. This is because the sugar coating is part of the protective coating of bacteria that protects them from the host’s defenses as well as viruses that often infect and kill bacteria. In tests on mice, the scientists were able to show that their new vaccine was more effective in preventing Salmonella infections than existing vaccines approved for use in pigs and chickens.
Scientists now plan to use the same principle to develop vaccines against other microorganisms – for example, against bacterial strains resistant to antimicrobials. In addition, it should be possible to use the biotechnology approach and make specific modifications in microorganisms by exerting selective pressure through vaccines.
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