Project description
Improved vaccines for older age
The goal of the EU-funded ISOLDA project is to develop novel vaccines against viral diseases for older age by promoting virus-specific T cell responses targeting T cell immunosenescence and inflamm-ageing. An international consortium will assess the potential of immunomodulators, including kinase inhibitors licensed for other applications, to improve vaccine-induced immune responses. The best selected compounds will be tested using in vivo animal models for vaccination against viral diseases. As clinical proof of concept, researchers will focus on improving the efficacy of influenza vaccines applying a lead immunomodulator compound selected from the ex vivo and in vivo studies to the current vaccine formulations. ISOLDA aims to provide innovative solutions to the age-related reduced efficacy in current preventive vaccines against viral infections for the increasing population of older adults.
Objective
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 SARS-CoV-2 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 proof of concept, ISOLDA will aim at improving the efficacy of a licensed vaccine against a respiratory virus, up to Phase I or II clinical trial with a lead immunomodulator compound or combination of compounds added to the vaccine formulations. The choice of Phase I or Phase II study design will depend on the compound, which will be selected based on results obtained upon prior in-vitro testing and in vivo testing in animal models. Promising SMKIs and/or oleic derivatives will be combined with a licensed MF59®-adjuvanted and a non-adjuvanted seasonal influenza vaccine for a Phase I, required to establish safety for this innovative combination. Alternatively, licensed MF59® will be selected as the lead compound, and administered as licensed seasonal influenza vaccines with and without MF59® and co-administered with licensed mRNA SARS-CoV-2 S vaccine. In this case, a Phase II study will be initiated to evaluate the immunogenicity in older adults aged 65 and older. ISOLDA will further build on new generation vaccines against MERS and/or COVID-19, 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.
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Funding Scheme
RIA - Research and Innovation actionCoordinator
30559 Hannover
Germany