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Among the greatest achievements of the 20th century, prolongation of life expectancy has been the result of improved health conditions, decreased childhood mortality, lower incidence of infectious diseases. The consequence is the rapid ageing of the world population, with the elderly representing over 25% of the entire population by the year 2030, of which 75% living in less developed countries. Ageing thus represents one of the major public health challenges of the 21st century. Indeed, unhealthy ageing and frailty of the aged population has an important impact on the economic development and social costs of a country, a problem even more acute in less developed countries. A better knowledge of immune senescence and the design of customised vaccination strategies for the elderly are the immediate challenges posed to scientists and physicians. The conference “Ageing and immunity”, recently held in Siena (Italy), has addressed these issues and defined the global strategic priorities for research and health policies aimed at ensuring healthy ageing.

Because of decreased immune functions of older people booster intervals of 3 years - instead of 5 - are recommended for tick-borne encephalitis (TBE) vaccinations for persons >or=60 years in Austria. So far, no comparative data on the immune-responsiveness of the age group 50-59 years are available. We therefore investigated the antibody titers and booster responses (in ELISA and neutralization assays) for the age groups 50-59, 60-69, and >69 years in comparison to a control group below 30 years. The age group 50-59 years displayed the same decreased antibody response, also characteristic for persons 60 years and older. Although antibody concentrations were lower after 5-7 years compared to 3-4 year intervals, antibodies were still detectable and could be sufficiently increased by booster shots in the vast majority of persons. Our results clearly indicate that the responsiveness of the immune system to vaccination is already impaired at the age of 50.

The stimulatory properties of soluble recombinant influenza nucleoprotein (NP) on purified CD4(+) and CD8(+) T cells from young and elderly individuals were studied. Recombinant influenza NP failed to induce proliferation of resting CD4(+) and CD8(+) T cells in the absence of IL-2. Addition of small amounts of IL-2, however, led to strong proliferation of resting CD4(+) and CD8(+) T cells from young and elderly donors. NP-reactive CD4(+) and CD8(+) T cell lines from both age groups grew equally well under long-term culture conditions. T cell lines raised to live influenza virus could recognize recombinant influenza NP and showed a substantial proliferative response. Stimulation of CD8(+) T cells is presumably due to cross-presentation, as EBV-transformed MHC class I-positive cell lines, which are incapable of antigen processing, stimulated live influenza virus-reactive CD8(+) T cell lines when loaded with NP-derived immunodominant peptides but not following loading with the whole NP molecule. Vaccines containing recombinant influenza NP might confer cross-protective immunity and could therefore be especially useful in cases of major epidemics or pandemics.

Streptococcus pneumoniae is a major human pathogen, causing high morbidity and mortality in children, and also in the elderly, who are particularly susceptible to S. pneumoniae infections due to the dysregulated function of the aged immune system. As the current generation of polysaccharide vaccines do not provide sufficient protection for elderly, new vaccination strategies are urgently needed. To learn whether pneumococcal proteins are able to induce adaptive immune responses in adults in different age groups, we determined serum IgG antibody titers and T cell immunity (IFN-γ, IL-17A and IL-5 production) to three pneumococcal antigens, PcsB, StkP and PsaA, that are components of an investigational protein-based pneumococcal vaccine, IC47. Therefore, sera and PBMCs of 108 healthy adults in three different age groups (young, middle-aged and elderly) were analyzed by ELISA and ELISpot, respectively. We found naturally acquired antibodies to all three proteins in all age groups against all three antigens. However, elderly individuals had significantly lower IgG levels to PcsB and PsaA compared to those of younger donors. There was no significant age-related difference in the overall rate of T cell immunity for the three pneumococcal proteins. We found that the Th17 response was dominant in all age groups and was frequently combined with a Th1 or Th2 response in young and middle-aged subjects. However, in elderly persons there was a lower percentage of PBMC samples producing more than one cytokine upon antigenic stimulation. The narrow cytokine secretion pattern was the most striking difference between elderly and younger adult age groups. Our results demonstrate that in the majority of adults there is a naturally acquired humoral and cellular immune response to the three pneumococcal proteins tested. The dominance of the Th17 response is especially interesting in the light of new insights regarding the role of Th17 cells in mucosal protection against this pathogen.

Among the greatest achievements of the 20th century, prolongation of life expectancy has been the result of improved health conditions, decreased childhood mortality, lower incidence of infectious diseases. The consequence is the rapid ageing of the world population, with the elderly representing over 25% of the entire population by the year 2030, of which 75% living in less developed countries. Ageing thus represents one of the major public health challenges of the 21st century. Indeed, unhealthy ageing and frailty of the aged population has an important impact on the economic development and social costs of a country, a problem even more acute in less developed countries. A better knowledge of immune senescence and the design of customised vaccination strategies for the elderly are the immediate challenges posed to scientists and physicians. The conference "Ageing and immunity", recently held in Siena (Italy), has addressed these issues and defined the global strategic priorities for research and health policies aimed at ensuring healthy ageing.

Summary In order to analyze the clinical impact of immunological alterations in thymectomized children after exposure to a new antigen (tick-borne encephalitis virus (TBEV) vaccine), 17 thymectomized children completed a three-dose immunization regimen. Thymectomized children showed significantly lower TBEV IgG antibody levels after the second vaccination when compared to healthy age-matched controls ( n = 30) ( p = 0.03), but a normal response after the third vaccination. Age at thymectomy correlated significantly with the TBEV IgG antibody levels ( p = 0.04). Thymectomized children also showed significantly lower total counts and percentages for naive T cells correlating with time after thymectomy ( p = 0.02), than observed for controls. These changes in T cell subsets and the decreased ability to respond to new antigens in thymectomized children, as observed here, may precede more striking effects such as higher infection rates or autoimmune conditions as they age.

Background Recent retrospective studies demonstrate that elderly persons have a shortened protection period following vaccination with recall antigens. Methods We now analysed the effect of booster vaccination with a multivalent vaccine containing tetanus, dipththeria, pertussis and polio antigens in 252 healthy elderly persons. The magnitude of the humoral immune response was assessed by antibody measurements. Results Comparison with a small control group of 21 younger persons demonstrates that pre- and post-vaccination antibody concentrations are lower in elderly persons for all antigens except polio, for which higher pre- and similar post-vaccination antibody levels are observed. Using multiple linear regression analysis we also show that the magnitude of the humoral immune response in elderly persons greatly depends on pre-vaccination antibody concentrations in the case of tetanus, diphtheria and pertussis, but much less so in the case of polio, against which priming and preceding booster immunizations were performed with attenuated live vaccine. Conclusion Regular booster vaccinations throughout life are of clinical importance to maintain the ability to respond to recall antigens in old age. Longer lasting protection and good responsiveness to boosting in spite of low antibody titres can be expected following exposure to live vaccine earlier in life.

Little information is available on post-vaccination antibody concentrations and the duration of protection in persons of more than 20 years of age. We, therefore, measured antibodies specific for tetanus (TT) or tick-borne encephalitis (TBE) virus in 734 adults (age 18-93 years, 382 females and 352 males) and evaluated these data in connection with the time point of the last vaccination against tetanus or TBE and age. This analysis revealed that the time of the last vaccination as well as age had highly significant effects on tetanus and TBE titers (p < 0.001). Our results show a strong decline in post-vaccination antibody concentrations with age, which sets in at the age of 40 in the case of tetanus, and is observed right throughout adult life in the case of TBE. Persons over 60 years of age frequently do not have protective antibody concentrations. We conclude that immunological responsiveness to vaccination decreases throughout adult life, and that conventional vaccination strategies designed for children and young adults cannot be uncritically applied in the elderly.

By definition, diseases of aging become clinically manifested in elderly patients. However, their pathogenetic basis has to be sought earlier in life. The general thread of this presentation relies on the concept of an evolutionary-Darwinian view of the development of age-related diseases. In essence, this concept states that we may have to “pay” for genetic traits that play a beneficial role earlier in life by the later development of diseases since there is no post-reproductive selective pressure that may have eliminated the potential late onset detrimental effects of such genes. Examples for this kind of trade-off are taken from diseases involving the immune system (infections), the endocrine system (andropause), the nervous system (Alzheimer’s disease), the locomoter system (osteoporosis), the cardio-vascular system (atherosclerosis) and cancer.

Dendritic cells (DC) are powerful antigen presenting cells, which have the unique capacity to stimulate naive T cells. In spite of the well-known decline of T cell function in old age, little information is available on whether DC are also affected by the aging process. This is mainly due to problems with the isolation and purification of DC. Rapid progress in the characterization of DC has been made in recent years, as simple methods to generate large numbers of DC from precursors have been developed. It was the aim of the present study to compare monocyte derived DC from old and young healthy persons. The generation of DC from blood monocytes in response to GM-CSF and IL-4 treatment was similar in cells from young and old persons. The DC population thus obtained had a typical dendritic morphology and expressed DC surface markers, such as HLA class II, CD1a, CD11c, CD54, CD80 and CD86, but not CD14 for a period of up to three weeks in culture. DC from young and old persons produced IL-12 and TNF-alpha and responded equally well to maturation-inducing stimuli. DC maturation was stimulated by purified protein derivative (PPD) of Mycobacterium tuberculosis, whole inactivated influenza virus and by influenza split vaccine, but not by purified viral RNA. When tested for their antigen-presenting capacity, DC from young and old persons were capable of stimulating the proliferation and the cytokine production of T cells. It was of particular interest that CD45RA(+) as well as CD45RO(+) T cells from aged donors were unable to respond to stimulation with influenza proteins presented by monocytes, but were triggered to proliferate and to produce cytokines when antigen was presented by DC. The results demonstrate that DC from old persons (a) may still function as powerful antigen-presenting cells provided the right differentiation and maturation stimuli are present; (b) are capable of mobilizing residual capacity in senescent T cells and (c) may therefore represent a potent tool for immunotherapy and vaccines in old age.

Cellular as well as humoral immune reactivity were studied in healthy young (30 years; n = 12) and older (65 years; n = 12) individuals before as well as 1 month after immunization with a trivalent whole virus influenza vaccine. Before vaccination, peripheral blood mononuclear cell proliferation in response to in vitro stimulation with each of the virus strains was low in both groups. No antibodies against either the H1N1 or the B strain were found in most individuals, while 91% of the young and 75% of the elderly persons had low but protective antibody titres to the H3N2 strain. Vaccination led to a significant enhancement of peripheral blood mononuclear cell reactivity to all three influenza strains in both age groups. However, there was a significant difference in the humoral immune response between the groups. While there was a vigorous antibody response to all three vaccine strains among young persons, protective titres against the H1N1 and the B strains were only just reached in the old. In contrast, antibody production to the H3N2 strain was most abundant in the majority of elderly individuals, leading to significantly higher titres in the old than in the young group. In conclusion, the results demonstrate the preferential induction of antibodies to one particular influenza strain despite equal T cell recruitment to all vaccine strains in healthy aged individuals after immunization with a trivalent influenza vaccine. Our findings underline the complexity of immunological alterations to be expected after vaccination in healthy elderlies.

The international consensus "Tick-borne encephalitis in childhood" was an important and successful achievement of the International Scientific Working Group on Tick-Borne Encephalitis (ISW TBE) [1]. The main topic of the 2005 conference meeting was "Tick-borne encephalitis in the golden agers". "Golden agers" is the synonym for people over 50 years of age. Still the incidence of TBE is underestimated, even in countries where the disease is known and there must be European regions where TBE occurs and is not yet diagnosed properly. Increasing mobility and the changes in lifestyle of people during the last 10 to 15 years, also in the age group over 50 years, have exacerbated the risk and the number of infections. In order to get more information about tick-borne encephalitis in older ages, data of seven European countries were presented (Austria, Croatia, Czech Republic, Germany, Lithuania, Poland and Sweden). Based on the scientific findings adequate conclusions were drafted by the ISW TBE.