Why vaccinations "work" for decades

Scientists from the University of Erlangen-Nuremberg (FAU) and the Erlangen University Hospital have tried to answer a simple question: why immunity after some vaccinations lasts for decades and sometimes for a lifetime. Their conclusion sounds surprisingly clear: the "longest-lived" immune cells are not those that work at their maximum, but those that go into energy-saving mode early and can persist for a very long time. The results are published in Nature Immunology.

The researchers chose yellow fever vaccination as a model - it is one of the most successful examples: in many people, a single vaccination is enough for very long-lasting protection. The team monitored the immune system response in dozens of healthy volunteers for a year after vaccination, and compared these data with blood samples from people vaccinated 7-26 years ago.

The main protagonists of the work were T-lymphocytes (CD8+ T-cells) - cells that help destroy virus-infected cells. After vaccination, the necessary T cells multiply rapidly, but then most of the "army" disappears. Only memory cells remain, which are able to switch on quickly when the virus is encountered again.

The researchers measured in detail how actively different subtypes of T-cells work (including the rate of protein synthesis and signs of energy metabolism). It turned out that a special group - the so-called naive-like memory T cells (TNM) - remains the least "expendable" in terms of energy, relies mainly on mitochondrial respiration and it is it that preferentially persists decades after vaccination (in the study - up to 26 years).

The authors interpret this to mean that long immune memory holds on "metabolic rest " - the ability to slow down in time and live "in low gear" while remaining ready to multiply rapidly when threatened again. This may help future vaccines and immunotherapies to be more precisely designed to better mould just such long-lasting memory cells.