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Why live vaccines may be most effective for preventing Salmonella infections

last modified May 27, 2016 11:53 AM
Vaccines against Salmonella that use a live, but weakened, form of the bacteria are more effective than those that use only dead fragments because of the particular way in which they stimulate the immune system, according to research from the University of Cambridge published today.

The BBSRC-funded researchers used a new technique that they have developed where several populations of bacteria, each of which has been individually tagged with a unique DNA sequence, are administered to the same host (in this case, a mouse). This allows the researchers to track how each bacterial population replicates and spreads between organs or is killed by the immune system. Combined with mathematical modelling, this provides a powerful tool to study infections within the host. The findings are published today in the journal PLOS Pathogens.

“We effectively ‘barcode’ the bacteria so that we can see where in the body they go and how they fare against the immune system,” explains Dr Pietro Mastroeni from the Department of Veterinary Medicine at the University of Cambridge, who led the study. “This has provided us with some important insights into why some vaccines are more effective than others.”

The multidisciplinary research team led by Dr Mastroeni used the new technique to look at the effectiveness of vaccines against infection by the bacterium Salmonella enterica, which causes diseases including typhoid fever, non-typhoidal septicaemia and gastroenteritis in humans and animals world-wide. Current measures to control S. enterica infections are limited and the emergence of multi-drug resistant strains has reduced the usefulness of many antibiotics. Vaccination remains the most feasible means to counteract S. enterica infections.

There are two main classes of vaccine: live attenuated vaccines and non-living vaccines. Live attenuated vaccines use a weakened form of the bacteria or virus to stimulate an immune response – however, there are some concerns that the weakened pathogen may become more virulent when used in patients with compromised immune systems, for example people infected with HIV, malaria or TB. Non-living vaccines, on the other hand, are safer as they usually use inactive bacteria or viruses, or their fragments – but these vaccines are often less effective. Both vaccines work by stimulating the immune system to recognise a particular bacterium or virus and initiate the fight back in the event of future infection.

Using their new technique, Dr Mastroeni and colleagues showed that live Salmonella vaccines enhance the ability of the immune system to prevent the bacteria from replicating and spreading to other organs. They can also prevent the spread of the bacteria into the bloodstream, which causes a condition known as bacteraemia, a major killer of children in Africa. Read more..