Project Detail |
ISOLDA aims at the development of improved vaccines for older adults against viral diseases with highest burdens at old age, by promoting virus-specific T cell responses in vaccinees over 65 years, using modulators of T cell immunosenescence and inflammageing. It builds on leading interdisciplinary expertise and knowledge of ISOLDA partners in virology, (onco-)immunology, ageing and immunosenescence, to assess the potential of immunomodulators, including kinase inhibitors licenced for other human use, to improve vaccine-induced immune responses and safety in older adults. ISOLDA partners have shown that these compounds may indeed restore key immunosenescent signatures. They will investigate ex-vivo signatures of immunological ageing and restoring potential of selected compounds on vaccine-induced immune responses against influenza virus, using PBMC from past and on-going adult and ageing human cohorts of influenza vaccinees. Cohorts of vaccinees and/or patients for tick-borne encephalitis, Middle-East respiratory syndrome and yellow fever are also uniquely available to ISOLDA to demonstrate broad applicability of the approach. The most promising compounds will be tested in in-vivo animal models for vaccination against these diseases. As a clinical proof of concept, ISOLDA will aim at improving efficacy of current seasonal influenza vaccines up to a tiered phase I clinical trial with a lead immunomodulator compound selected from the ex vivo and in vivo studies, that will be added to current vaccine formulations. ISOLDA will further build on new generation vaccines against MERS, such as replication-competent propagation-deficient replicons and MVA-MERS S recently developed by ISOLDA partners. Taken together, ISOLDA will address call SC1-BHC-14-2019, by providing innovative solutions to reduced efficacy and safety of preventive vaccines in the increasing population of older adults, against viral infections that have the highest impact in this age group. |