Development of adapted vaccination strategies for directed stimulation of senescent immune cells using in vitro models

Arne Müller1,4, Marcus Frohme2, Stefan Lüth3, Werner Dammermann3, Joachim W. Dudenhausen4, Katja Hanack1

1 University of Potsdam, Institute of Biochemistry and Biology, Karl-Liebknecht-Str. 24-25, 14476 Potsdam

2 Technical University of Applied Science Wildau, Faculty of Engineering and Natural Science, Hochschulring 1, 15745 Wildau

3 Brandenburg Medical School Theodor-Fontane, University Hospital Brandenburg, Center of Internal Medicine II, Hochstraße 29, 14470 Brandenburg an der Havel

4 Faculty of Health Science Brandenburg, Location University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam

Due to demographic changes the average age of the human population will drastically increase within the next decades. This will put a huge pressure on health systems all over the world. Therefore, one major issue is to keep aged adults healthy by using vaccinations. However, during aging the human immune system underlies characteristic changes, called immunosenescence. Thereby, immune processes, e.g. development, maturation and migration, are affected negatively which leads to a decreased potency of vaccines in elderly people. Therefore, the characterisation of immune cells from elderly people and the development of new vaccines or vaccination strategies are of crucial importance. In this study, we investigated the general blood count from younger (<25 years) and older (>65 years) persons and showed that there were almost no differences in the number monocytes/macrophages (~15-16 %) and dendritic cells (~13-14 %) but the amount of T and B cells were reduced. A reduction of about 30 % was detected for T cells and about 60 % for B cells. The study focused further on the characterisation of in vitro generated monocytes-derived dendritic cells (moDCs) from younger and older persons. After the isolation, CD14+ cells were differentiated into moDCs for 7 days. Both groups showed a similar result. About 89 % (young persons) and 83 % (old persons), respectively, expressed CD209. Furthermore, the phagocytic uptake and degradation of antigen showed slight but no significant differences between both groups. The moDCs of the elderly phagocytosed and processed the model antigen DQ-OVA slightly faster than compared to the younger group during the first 10 min of incubation. After 15 min, in both groups over 90 % of the mo-DCs showed a fluorescence signal with similar intensity. Finally, the analysis of expression levels of co-stimulatory and maturation markers is also similar in both groups. On the one site, all moDCs do express CD40 and HLA which were upregulated upon stimulation. Both are slightly, but not significantly, upregulated in the groups of the elderly. On the other site CD80 and CD86 is almost not upregulated in both groups. Nevertheless, the amount of cells which did express those co-stimulatory receptors was increased. Interestingly in younger persons, both are slightly but not significantly  upregulated. No significant differences between moDCs from younger and older persons were seen concerning differentiation, phagocytosis and processing of antigen as well as upregulation of co-stimulatory and maturation markers. Therefore, moDCs would be a promising target for new vaccination strategies for elderly people.

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