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09/30/2024 15:39
Why the flu shot is less effective in older people
CiiM study identifies key molecules and possible approaches to improve vaccination response
There are so-called high-dose flu vaccines for older people. The reason: Your immune system does not always respond sufficiently well to the standard flu vaccines. Why this is the case and what molecular processes are behind it is still not understood. In their current research work, a cohort study with around 230 participants over the age of 65, scientists from the Center for Individualized Infection Medicine (CiiM), a joint institution of the Helmholtz Center for Infection Research (HZI) and the Hannover Medical School (MHH) , but now identify crucial key molecules. The researchers hope that their results will help to further increase the immune response to the flu vaccination in older people in the future. The study was published in the journal “Science Advances”.
Every year at the beginning of October the time has come: the flu wave is on its way. “Because older people in particular have an increased risk of a severe course of the disease, effective vaccines are particularly important for them,” says Prof. Yang Li, Scientific Director of CiiM and Head of the “Bioinformatics of Individualized Medicine” department at the HZI. There are so-called high-dose flu vaccines for people aged 60 or 65 years and over because the standard flu vaccines do not work sufficiently well for them. But why is that so? “With age, the immune system is obviously no longer able to mount such a powerful immune response,” explains Li. “With our study, we wanted to find out exactly what this is connected to, which molecular processes play a role here – and identify approaches that can improve the immune response could become.”
The study was based on a cohort of 234 participants over the age of 65 who were vaccinated against influenza. Blood was taken from them at a total of five different times – before and after the vaccination. This was examined in detail using the most modern molecular biological methods, which are summarized under the term “multi-omics”. The researchers analyzed the huge amounts of data generated using statistical and computer models. They investigated the question of how the immune response differs between those who respond well to the vaccination (responders) and those for whom the vaccination does not work (non-responders). “We were able to identify a number of important molecules that correlated with the good immune response of responders after vaccination. In the non-responders, however, they were reduced or not present at all,” explains Dr. Saumya Kumar, scientist in Yang Li’s group at CiiM and first author of the study. “And unlike the responders, the non-responders showed an increased number of certain activated immune cells in the blood, so-called natural killer cells. The differences we were able to identify between responders and non-responders at various levels of assessment were actually very clear.”
In their study, the scientists also examined the question of whether it is possible to predict how good the immune response will be before vaccination. “To do this, we looked at the blood samples that were taken before the vaccination. The later non-responders had elevated levels of interleukin-15 before vaccination. “High levels of this messenger substance can be an indication of developing chronic inflammatory processes in older people,” says Li. In subsequent studies in mouse models, the researchers were able to show that mice that lacked the receptors for the messenger substance had an improved response to immunization . “Interleukin-15 is obviously responsible for the lack of an immune response and could therefore be well suited as a predictive biomarker,” says Li. “It would also be conceivable to reduce increased levels of interleukin-15 before vaccination by administering suitable active substances in order to reduce the immune response to improve. But such an approach is actually still a thing of the future.”
The scientists showed another interesting approach in their study: the non-responders had significantly lower concentrations of long-chain fatty acids in their blood before the vaccination than responders. “Older people often suffer from comorbidities that are associated with chronic inflammatory processes. Certain long-chain fatty acids have an anti-inflammatory effect and overall support the development of a good immune response,” says Kumar. “An adequate supply of long-chain fatty acids, such as those found in fish oil or healthy nuts, could be an effective way to improve the immune response to flu vaccinations in addition to general health. Whether and how well this works still needs to be researched.”
“With our study, which for the first time included such a large cohort of participants from the over-65 age group, we were able to provide important insights into the formation of the vaccination response after a flu vaccination in older people,” says Li. “We were able to identify key molecules for Identify good or bad immune responses that can be used for further research. We hope that our research results can help to further increase the immune response to flu vaccinations in older people in the future.”
The study was carried out in cooperation with the MHH and the TWINCORE, Center for Experimental and Clinical Infection Research, a joint institution of the HZI and the MHH, and the University of Lisbon, Portugal. The research was supported by the ERC Starting Grant ModVaccine (948207) awarded to Yang Li.
Text: Nicole Silbermann
The Helmholtz Center for Infection Research:
Scientists at the Helmholtz Center for Infection Research (HZI) study bacterial and viral infections as well as the body’s defense mechanisms in Braunschweig and other locations in Germany. They have in-depth specialist knowledge in natural product research and their use as a valuable source for novel anti-infectives. As a member of the Helmholtz Association and the German Center for Infection Research (DZIF), the HZI conducts translational research to create the basis for the development of novel therapies and vaccines against infectious diseases. http://www.helmholtz-hzi.de
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Original publication:
Saumya Kumar et al. Systemic dysregulation and molecular insights into poor influenza vaccine response in the aging population.Sci. Adv.10,eadq7006(2024).
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