Major achievements

Vaccination is the most effective measure to prevent infectious diseases. Childhood vaccination programs led to a dramatic decrease of infections in children. As the incidence and severity of many infections are high in the older population, this age group is an important target group for vaccination. Many currently used vaccines are less immunogenic and less efficient in the elderly compared to younger adults. In addition to the vaccines specifically targeting the older population (influenza, S. pneumoniae, herpes zoster), vaccination recommendations for adults include regular booster shots against tetanus, diphtheria and pertussis every 10 years. Vaccination against tick-borne encephalitis (TBE) and regular booster immunizations every 5 years are recommended in endemic areas such as Austria. Austrian guidelines include shortened booster intervals for persons older than 60.

We have shown that protective antibodies against tetanus can be detected in most adults, but protection against diphtheria is frequently insufficient. Booster vaccination restores protection against diphtheria only for a limited amount of time, and five years after a booster vaccination, antibody levels had dropped below the protective limit in approximately half of our older cohort. Similar results were obtained after a second booster vaccination. Vaccination history and antibody levels are very heterogenous throughout Europe, but in the six countries we investigated, older adults had consistently lower antibody levels compared to young adults. Investigating TBE-specific antibody concentrations in young and older adults several years after their last vaccination, we could show that antibody titers are lower in older compared to younger adults and decline over time. Interestingly, low antibody concentrations were already found in persons aged 50-60 years. Upon booster vaccination all age groups responded with an increase in antibody concentrations, but still all age groups above 50 years had lower titers than the younger cohort. Hepatitis B vaccine is administered to adults as a travel vaccine and to specific risk groups (e.g. medical personnel). This also includes older adults. We show that immune responses to booster vaccination against hepatitis B are similar in young and older adults, whereas primary responses are delayed and impaired in the older age group. Specific early transcriptional changes were identified, which correlated with vaccine responsiveness during primary and booster vaccination. As part of a large European consortium (VITAL, we are currently investigating immune responses after influenza and pneumococcal vaccination in different age group. The VITAL project aims to address this challenge by assessing the ID burden and mechanisms of immunosenescence to provide evidence-based knowledge on vaccination strategies to establish healthy ageing.

In addition to our work on vaccination we focus on age-related changes in the function of the adaptive immune system, mainly on T cells. Most studies on human immunosenescence use peripheral blood. However, antigen-experienced adaptive immune cells migrate back to the bone marrow. We characterized age-related changes of the T and B cell compartment in human bone marrow, which are distinctly different from the situation in peripheral blood, highlighting the importance of the source of immune cells for studies on immunosenescence. Highly differentiated effector T cells share some properties with senescent cells (short telomers, DNA damage, metabolic changes), but they are still able to proliferate if provided with adequate stimulation and can therefore not be considered “truly” senescent. There is still no consensus in the field on whether there is a truly senescent subset of T cells, how to define and identify such a subset, and its biological role. Traditional aging research is frequently centered around cellular or replicative senescence, whereas the field of immunosenescence concentrates on differentiation states and exhaustion of T cells, and we aim to bridge these two concepts.

We investigate a recently discovered subset of CD8+ HLA-DR+ regulatory T cells, which accumulate with age, but seem to lose their regulatory functions. Aspects we address include their impact on T cell function beyond their suppressive effect on proliferation, their interplay with other immune cells, e.g. antigen-presenting cells and the elucidation of the molecular mechanisms behind these functions. CD4+ regulatory T cells also accumulate with age and are involved in the development of age-associated diseases. The phenotype and functionality of regulatory T cells in aging is not well characterized, and we recently started to investigate this cell type. In addition to the “classical” regulatory functions of this cell type we want to study metabolic changes like the shift between glycolysis, which is utilized by regulatory T cells for proliferation and migration, and oxidative metabolism, which is essential for their suppressive functions, in the context of aging. First experiments have been started to look at the interplay of CD4+ and CD8+ regulatory T cells.

In-dept understanding of immunological processes in older adults is crucial for the development of strategies to delay immunological aging as well as for optimal therapeutics and vaccines for this age group.


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