Assessing the safety of future vaccines

Researchers have identified a set of genes that indicates whether a potential vaccine will cause a strong inflammatory response in mice.

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Measles, whooping cough and other diseases can cause serious illness and death in humans, especially in young children and other vulnerable individuals. Giving people vaccines ‘trains’ their immune system to recognize and fight the microbes that cause the conditions.

During an infection, the immune system triggers a set of responses that limit the spread of the infectious agent and eliminate it from the body. This can include swelling of tissues (known as inflammation), which in rare cases, can be life threatening.

Inoculations work by sparking a mild immune response in the body. Before a new vaccine is licensed for use, it is thoroughly tested in mice and rodents, and then in human volunteers, to ensure it will cause little or no inflammation. Finding a way to predict early on whether a vaccine candidate will trigger dangerous levels of inflammation would improve this process.

To explore this, McKay, Cizmeci et al. injected the muscle tissue of different groups of mice with one of four licensed vaccines which, by definition, cause little or no inflammation. Other groups of animals were given one of three drugs known to trigger inflammation. Over the following seven days the team repeatedly collected blood as well as cells from the muscle tissue and the lymph nodes. These samples were then analysed to find out which genes were switched on or off at any given time.

The experiments show that the responses of genes in the blood and lymph cells of the mice are connected to those in the muscle cells. Therefore, blood samples may provide a quick and convenient way to assess how an animal is responding to a potential new vaccine. By comparing the genes switched on or off in response to the different vaccines and drugs, McKay, Cizemeci et al. were able to identify a set of genes (known as “biomarkers”) that are associated with inflammation in animals. These biomarkers can be used to spot early on whether a new treatment is triggering inflammation.

The next step would then be to identify a similar or identical set of biomarkers in other animals used in vaccine research, and in humans. Ultimately, this approach could make the assessment of the safety of a new vaccine candidate easier.