Periodic Reporting for period 4 - TRAIN-OLD (Trained immunity: improving the next generation of vaccines for the older generation)
Berichtszeitraum: 2024-04-01 bis 2024-09-30
The efficacy of vaccination is dependent on the age of the person who is vaccinated. Unfortunately, individuals of older age have a less efficient immune response after vaccination, leading to less protection against infections. This is due to accumulated defects during the process of aging in the immune cells that are generally targeted by vaccines: the lymphocytes. These defects are seen in the population during the vaccination against important infections such as influenza (flu) or pneumococcus pneumonia. In contrast to the lymphocytes, the function of other immune cells remains normal also in patients of older age. These cells form another arm of the host defense, so-called ‘innate immunity’, and can also provide important protection against infections. The aim of the TRAIN-OLD project is to identify the immune cells from innate immunity that can be also stimulated by vaccines, try to identify new methods of boosting their activity in the older individuals, study the factors that influence these effects, with the overall aim to lead to a new generation of better vaccines in the future (Figure). Such new generation of vaccines would have an increased effectiveness in the older individuals compared to the vaccines currently available.
Innate immune responses are mediated by several types of immune cells, and the first aim of the project was to identify precisely which of these immune cells can be activated by the vaccines, and could be thus good candidates for increased function by the future vaccines. We have identified several of the innate immune populations from the blood which can be very effectively activated by certain types of vaccines, and also the mechanisms through which this activation takes place. In addition to that, in additional studies we have investigated whether the time of the day and the season of vaccination is also important for these effects. Indeed, this seems to be the case, fact that has important consequences for the public health measures necessary during vaccination campaigns.
In additional studies, we have also investigated the importance of the diet and lifestyle of the volunteers for the induction of immune cell activation. We have observed that unhealthy lifestyles lead to immune cells that are continuously inappropriately activated, and that can induce on the one hand inflammatory diseases, but on the other hand can reduce the effectiveness of vaccination. These data underline the importance of a balanced diet and a healthy lifestyle.
Finally, we have used this information and designed clinical trials in which vaccines that activate innate immune cells are tested for their capacity to protect elderly individuals against infections. In one such trial performed just before the COVID-19 pandemic, the BCG vaccine (that is usually used against tuberculosis) has been shown to decrease also the prevalence of other infections by 40%. Subsequently, similar studies have been designed and performed during the COVID-19 pandemic, with the results showing that while the total number of COVID-19 infections was not modified, the severity of the infection and the mortality was decreased by BCG vaccination.
In additional studies, we have also investigated the importance of the diet and lifestyle of the volunteers for the induction of immune cell activation. We have observed that unhealthy lifestyles lead to immune cells that are continuously inappropriately activated, and that can induce on the one hand inflammatory diseases, but on the other hand can reduce the effectiveness of vaccination. These data underline the importance of a balanced diet and a healthy lifestyle.
Finally, we have used this information and designed clinical trials in which vaccines that activate innate immune cells are tested for their capacity to protect elderly individuals against infections. In one such trial performed just before the COVID-19 pandemic, the BCG vaccine (that is usually used against tuberculosis) has been shown to decrease also the prevalence of other infections by 40%. Subsequently, similar studies have been designed and performed during the COVID-19 pandemic, with the results showing that while the total number of COVID-19 infections was not modified, the severity of the infection and the mortality was decreased by BCG vaccination.
The TRAIN-OLD project has achieved several important milestones that bring the knowledge regarding vaccination beyond what is currently known. In this respect, the discovery of certain types of immune cells that function normally in individuals of older age is new and extremely important for vaccine design. In addition, we have identified molecular mechanisms that act at the level of the cell itself, that explain these effects and that can be stimulated in the future to improve activation of the immune system. The discovery that certain vaccines can improve the general immune status and host defense of individuals of older age can have great importance for future use of vaccines.
During the project, we have obtained important new insights regarding the factors influencing response to vaccination in the elderly. We have thus identified genetic, epigenetic and environmental factors that influence the response of the elderly individuals to vaccines. These new insights obtained in understanding the response of the older individuals to both infections and vaccination can be therefore used for future therapies for both infections, as well as other important diseases characterized by a poor immune response in the elderly, such as cancer.
During the project, we have obtained important new insights regarding the factors influencing response to vaccination in the elderly. We have thus identified genetic, epigenetic and environmental factors that influence the response of the elderly individuals to vaccines. These new insights obtained in understanding the response of the older individuals to both infections and vaccination can be therefore used for future therapies for both infections, as well as other important diseases characterized by a poor immune response in the elderly, such as cancer.