Experimental vaccine forces bacteria into an evolutionary deadlock
Pathogens like bacteria and viruses evolve extremely well in response to drugs, which can make vaccines ineffective. But now ETH Zurich researchers have found a way to arm this ability against them, forcing the bugs into harmless evolutionary dead ends.
Microbes are living examples of evolution in action. Classic Darwin’s theory says that when life forms are exposed to the pressures of their environment, some of them will develop new genetic mutations that will help them cope better. As other individuals will be disadvantaged, mutations will eventually become the norm across an entire population.
In the world of bacteria and viruses, drugs and vaccines are the environmental pressures they must overcome. And they do it with frustrating ease, quickly finding ways to sidestep attacks, then trading those genes like trading cards. The end result is the constant and looming threat of antibiotic resistant “superbugs” that render our best drugs ineffective.
The researchers at ETH Zurich therefore decided to turn this strength into a weakness. Rather than developing a drug that kills bacteria, the team wanted to find a way to channel its evolution down a path where it would become weaker and less problematic for the host.
To start, the team assayed groups of mice with several different vaccines against Salmonella typhimurium, then watched closely how bacteria in their intestines developed resistance to the drugs. Eventually, they were able to identify the full range of scalable escape routes that the Salmonella used to survive.
Then they combined four Salmonella strains in a vaccine that cuts off all of those escape options. And of course, the bacteria retreated into a new form where they were still able to multiply without the drug touching them. The compromise? the Salmonella could no longer infect host cells to cause disease.
“This has 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 human and veterinary medicine,” says Emma Slack, author. principal of the study. “We can use it to drive the evolution of pathogenic microorganisms in a certain direction – in our case, a dead end.”
Upon closer inspection, the researchers found that the reason for this weakness was that the sugar molecules on the bacteria’s surface had atrophied. This coating normally helps insects hide from the host’s immune system or viruses.
When researchers tested the technique on mice, they found that it offered animals better protection against Salmonella infections than existing vaccines.
The team says the technique could be used to develop new vaccines against antibiotic-resistant bacteria, and potentially even eliminate some dangerous strains in the same way smallpox was eradicated.
The research was published in the journal Natural microbiology and the team describes the work in the video below.
Spark Award 2020 – Scalable Trap Vaccines
Source: ETH Zurich