Scientists in Switzerland have developed a vaccine that sets a trap for a type of Salmonella.

Researchers at ETH Zurich and the University of Basel created the Salmonella vaccine that guides the evolution of intestinal bacteria in the gut to make them a weaker pathogen instead of trying to kill them.

“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. We can use it to drive the evolution of pathogenic microorganisms in a certain direction — in our case, a dead end,” said ETH Professor Emma Slack.

Developing vaccines against bacteria can be more difficult than for viruses. Bacteria are able to impact 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 so they become less transmissible or cause less damage. Some pathogens, including many bacteria, change in ways that allow them to escape the effects of vaccination while remaining highly infectious.

A past problem has been that developed vaccines against bacterial pathogens often quickly become ineffective.

Vaccine cocktail impact
Researchers inoculated mice with slightly different oral vaccines against Salmonella typhimurium, and observed how the Salmonella in the animals’ guts modified its genes to escape the vaccines’ effects. They then produced a combination vaccine from four Salmonella strains that covered all the bacteria’s genetic evasion options.

The combined version caused an important Salmonella sugar coating on the surface to decline. While affected bacteria were still able to multiply in the animals’ guts, they were largely unable to infect body tissues and cause disease. It is also thought to reduce transmission potential to other animals. The sugar coating is part of the bacteria’s protection that shields them from the host’s defenses and from viruses that often infect and kill the bacteria.

Antibiotics are still the main treatment to fight bacterial infections. However, because of extensive and sometimes improper use in human medicine and livestock farming, resistant pathogens are emerging, which don’t respond to antibiotic treatment. Breeding animals often suffer from diarrhea caused by Salmonella.

In tests on mice, scientists showed the new vaccine was more effective at preventing Salmonella infections than existing ones approved for use in pigs and chickens, according to the study published in the journal Nature Microbiology.

Salmonella Typhimurium evades the immune defense of the gut by modifying its cell surface molecules. The immune system struggles to keep up with this bacterial adaptation and cannot produce the antibodies needed to recognize these surface structures fast enough to neutralize the bacteria.

Scientists now plan to develop vaccines against other microorganisms such as antimicrobial-​resistant bacterial strains.

Médéric Diard, from the Biozentrum of the University of Basel, said microbes have good adaptation skills.

“They can change rapidly to cope with unfavorable living conditions. However, bacteria cannot foresee the long-term detrimental consequences of this adaptation. Our vaccine exploits this weakness.”

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