Age-associated changes in the immune system (immunosenescence) contribute to increased incidence and severity of infections and decreased immunogenicity and clinical efficacy of many currently used vaccines in older adults. We investigate how T cells change with age and study the immune responses after vaccination with licensed vaccines to develop improved vaccination strategies.

We focus on age-related changes in the function of the adaptive immune system, mainly on T cells. Highly differentiated effector T cells share some properties with “classical” senescent cells, including short telomeres, DNA damage, metabolic changes, and increased expression of pro-inflammatory molecules. Still, it is controversially discussed whether they can 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. In contrast, the field of immunosenescence concentrates on differentiation states and exhaustion of T cells, and we aim to bridge these two concepts. We also 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 elucidating 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 are 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.

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 older people than younger adults. In addition to the vaccines explicitly targeting the older population (Influenza, S. pneumoniae, Herpes zoster, Respiratory Syncytial Virus), vaccination recommendations for adults include regular booster shots against tetanus, diphtheria, and pertussis as well as tick-borne encephalitis (TBE) in endemic areas such as Austria.

We have investigated immune responses following booster vaccination against tetanus/diphtheria, demonstrating insufficient protection against diphtheria, particularly in older adults. I TBE-specific antibody concentrations are lower in older compared to younger adults several years after their last vaccination and decline over time. 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. As part of a large European consortium (VITAL, https://vital-imi.eu/), we are investigating immune responses after influenza and pneumococcal vaccination in different age groups. 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 aging.

A better understanding of the basic mechanisms of immunosenescence and in-depth analyses of vaccine-induced immune responses in older adults are crucial for developing optimal vaccines for this age group. In addition, life-long vaccination programs and increased awareness among stakeholders and the general public are essential for increased vaccine uptake and optimal protection of vulnerable groups.

Publications:

ORCID