major-achievements.html.en - major-achievements.html.en

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 elderly (influenza, S. pneumoniae, herpes zoster), vaccination recommendations for adults include regular booster shots against tetanus, diphtheria, pertussis and polio 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. 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.

Protective antibodies against tetanus can be detected in most adults, but protection against diphtheria is frequently insufficient. 65% of an older cohort did not have protective antibody concentrations against diphtheria at the time of enrollment and due to quickly waning antibody levels booster vaccination restores protection only for a limited amount of time. Five years after a booster vaccination antibody levels had again dropped below the protective limit in approximately half of the older cohort. Similar results were obtained after a second booster vaccination. A potential impact of latent CMV-infection (see below) on the success of vaccinations is discussed controversially in the literature. We observed no impact on the short-term antibody response after vaccination, which is the parameter analyzed by most studies, but interestingly, the decline of antibodies was more pronounced in CMV-positive compared to CMV-negative individuals suggesting an impact on long-term maintenance of antibody-producing plasma cells.

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.

 

Depending on age, geographical region, and socioeconomic background 30-100% of the adult population are infected with Cytomegolovirus (CMV), a human b-herpesvirus. Life-long latency is established after primary infection, which is usually asymptomatic or clinically mild in immunocompetent persons. Reactivation of latent CMV occurs frequently in immunocompetent persons, but does not lead to clinical symptoms, as the immune system is capable of controlling viral replication. T cells are essential for viral control and up to 25% of the total CD8⁺ T cell pool can be specific for CMV. An immunodominant HLA-A2-restricted epitope (NLVPMVATV) derived from the viral matrix protein pp65 has been described (CMV_NLV). The magnitude of the CMV-specific T cell response is remarkable compared to responses to other pathogens including other herpesviruses. We could demonstrate that CMV_NLV-specific CD8⁺ T cells preferentially use the V beta families 8 and 13. Within the V beta family 8 we identified a CDR3 sequence motif, which is shared by adult donors of all age groups and a second, distinct sequence motif, which only occurred in middle-aged and even more frequently in older adults, but was absent in younger donors. This age-associated clonotype shows higher avidity towards the peptide MHC-complex, and might contribute to the control of CMV reactivation despite age-related deficits of the immune response. Effector CD8⁺ T cells, which do not express the costimulatory receptor CD28, and naïve/early memory CD28⁺CD8⁺ T cells share the same CMV_NLV-specific T cell receptor clonotypes.

It has been described that latent CMV infection accelerates and aggravates age-related changes of the T cell compartment. In a large cohort of healthy older adults with a seroprevalence of 65% for CMV we could demonstrate that the changes induced by latent CMV infection are distinct from the purely age-related changes, particularly for the CD4⁺ T cell compartment and regarding correlations between CD4⁺ and CD8⁺ T cell populations. Immunosuppressive treatment e.g. after organ transplantation, frequently targets T cell function and proliferation. The effect of immunosuppressive drugs on T cells shows distinct differences in CMV-positive compared to CVM-negative patients after kidney transplantation.