New insights into how humans respond to vaccination are reported in a paper published online this week in Nature Immunology. The study finds a molecular signature that could help to identify people who might experience negative responses to immunization.

Adrian Hayday and colleagues immunized 178 healthy participants with a vaccine for ‘swine flu’-caused by a type of influenza virus (H1N1) that circulated in a major outbreak in 2009-that contained an additional compound designed to boost immune responses. They then measured hundreds of parameters that affect the responsiveness of the immune system in humans.

They found that within 24 hours, all volunteers showed profound changes in the frequencies of circulating white blood cells, as well as in the genes and proteins expressed by these cells, compared with their pre-vaccination state. They found notable differences between younger volunteers (<35 years of age) and older volunteers in this early immune response.

In the 20% of participants who reported adverse responses to vaccination, the authors detected an underlying pre-vaccination signature that correlated with increased frequencies of immature B cells in the blood. B cells are responsible for making antibody molecules, and transitional B cells, such as those identified here, have been associated with autoimmune diseases that affect joints or connective tissues. The authors found that autoantibodies were present in the samples obtained from these otherwise healthy subjects before they were immunized, which suggested this pre-existing condition might have contributed to the adverse response these participants experienced and might indicate that they could be at greater risk of developing autoimmune disease in the future.