Researchers at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Erlangen University Hospital have demonstrated why vaccinations often provide lifelong protection: Certain T cells switch to an energy-saving mode early on, thereby ensuring a stable immunological memory for decades. Using the yellow fever vaccine as an example, the study published in Nature Immunology demonstrates that metabolic dormancy is a fundamental principle of long-lasting immunity.
Why is the human immune system often able to remember a vaccination for a lifetime? Researchers at FAU and Universitätsklinikum Erlangenr have investigated this question. Their study shows that the T cells responsible for immunological memory switch to a kind of standby mode at an early stage. In this state, they can survive for many decades.
The yellow fever vaccine, one of the most effective examples of successful immunization in humans, served as the model system. Typically, a single injection is sufficient to achieve exceptionally strong and often lifelong protection. This makes the vaccine particularly well-suited for studying the development of stable immunity.
The study analyzed more than 50 healthy adults who had recently been vaccinated against yellow fever. Their immune response was monitored over the course of a year. In addition, the team examined blood samples from individuals who had been vaccinated seven to 26 years earlier. This allowed them to compare the characteristics of T cells shortly after vaccination with those they retain over the long term.
After vaccination, the T lymphocytes that recognize and fight virus-infected cells initially proliferate. A broad spectrum of specialized immune cells develops, most of which die off after successfully combating the pathogen. A small portion, however, persists as memory cells and ensures that the body can react more quickly upon renewed exposure.
Among other things, the researchers examined the metabolic rate of these yellow fever-specific T cells. They found that the cells that later form the immunological memory significantly reduce their metabolic activity at an early stage. This energy-saving mode ensures their long-term survival. Measurements of protein synthesis confirmed that it is precisely the long-lived cells that are characterized by consistently low activity.
This pattern was already evident in the first weeks following vaccination and remained stable for decades. Extensive bioinformatic analyses confirmed the long-term maintenance of this program. Additional studies in mouse models and in humans following SARS-CoV-2 vaccination showed the same correlation.
The results illustrate that sustained strong vaccine protection does not rely on constant peak performance. Rather, what is crucial is the ability of individual immune cells to switch to a resource-conserving state in a timely manner and thereby remain operational for many years.