THE so-called vaccineor high-dose flu shot is available for older people. The reason: Their immune systems don’t always respond well enough to the standard flu vaccine. Why this happens and the underlying molecular processes are not yet understood.
High-dose flu vaccine for older people
In their current research work, scientists from the Center for Individualized Infection Medicine (CiiM), a joint initiative of the Helmholtz Center for Infection Research (HZI) and the Medical Faculty Hannover (MHH), using a cohort study with around 230 participants over the age of 65, they have now managed to identify key molecules.
The researchers hope that their findings will help further boost the immune response to the flu vaccine in older people in the future. The study was published on Science Advances.
Every year at the beginning of October, the flu epidemic hits. “Given that 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 Department of Bioinformatics of Individualized Medicine at the HZI.
There is a so-called high-dose flu vaccine for people aged 60 or 65 and older, as the standard flu vaccine does not work well enough for them. But what is the reason?
“With age, the immune system is no longer able to develop a sufficient immune response,” explains Li. “With our study, we wanted to find out exactly what it is connected to, which molecular processes play a role here and identify approaches that could be used to improve the immune response.”
The study was based on a cohort of 234 participants over the age of 65 who had been vaccinated against influenza. Blood was taken from them at a total of five different times, before and after vaccination. This was examined in detail using the latest molecular biology methods, which are summarized under the term “multi-omics”.
The researchers analyzed the huge amounts of data generated using statistical and computational models. In doing so, they studied how the immune response differs between those who respond well to vaccination (responders) and those who do not (non-responders).
“We were able to identify a number of important molecules that correlated with the good immune response of responders after vaccination. In non-responders, however, these signature molecules were reduced or not detected at all,” explains Dr. Saumya Kumar, a scientist in Yang Li’s research group at CiiM and first author of the study.
“And unlike responders, non-responders showed increased numbers of certain activated immune cells in the blood, so-called Natural Killer cells. The differences that we were able to identify between responders and non-responders at various levels of omics layers were very clear indeed.”
In their study, the scientists also investigated whether it is possible to predict how good the immune response will be before vaccination. “To do this, we examined blood samples that were taken before vaccination. Subsequent non-responders showed elevated interleukin-15 levels before vaccination. Elevated levels of this messenger molecule may be an indication of the development of chronic inflammatory processes in older people,” says Li.
In subsequent studies conducted in the mouse model, the researchers were able to demonstrate that mice lacking receptors for the messenger molecule showed a better response to immunization.
“Interleukin-15 appears to be responsible for the lack of a sufficient immune response and could therefore be a good predictive biomarker,” says Li. “It would also be conceivable to reduce elevated interleukin-15 levels before vaccination by administering suitable active substances to improve the immune response. However, such an approach is still a long way off.”
The scientists also revealed another interesting approach in their study: subjects who did not respond to vaccination had significantly lower concentrations of long-chain fatty acids in their blood before vaccination compared to subjects who responded to vaccination.
Elderly people often suffer from concomitant diseases that are associated with chronic inflammatory processes. Some long-chain fatty acids have an anti-inflammatory effect and support the development of a good overall immune response,” says Kumar.
“An adequate intake of long-chain fatty acids, such as those found in fish oil or healthy nuts, could be an effective way to improve your immune response to flu vaccinations and overall health. Whether and how well this works remains to be studied.”
“With our study, which for the first time included such a large cohort of participants over 65 years of age, we were able to provide important information on the formation of vaccine response after influenza vaccination in older people,” says Li.
“We were able to identify key molecules for good and bad immune responses, which can be used for further research. We hope that our research findings can help further boost the immune response of flu vaccinations in older people in the future.”
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