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Trained immunity: improving the next generation of vaccines for the older generation

Project description

New vaccines train the immune system in older people

One of the challenges of old age is a dramatic decrease in the efficacy of vaccination, particularly where adaptive immunity is concerned when the immune system tries to eliminate specific pathogens. However, innate immunity (the general immune system response to pathogens) in the elderly remains relatively intact. This EU-funded project is focusing on the induction of innate immunity to improve vaccination efficacy in the elderly. Recently, project researchers discovered the trained immunity phenomenon, when certain vaccines and mild infections induce reprogramming of innate immunity cells for a subsequent strong general immune response to pathogens. The current project aims to understand the cellular and molecular pathways of trained immunity responses, and enable the development of better vaccines for the elderly.

Objective

The host defense, especially the adaptive immunity, is defective in the elderly, with a dramatic drop for the efficacy of vaccination with old age. Interestingly however, the innate immunity of older individuals is relatively intact, and we recently described that epigenetic and functional reprogramming of innate immune cells by certain vaccines and mild infections, termed ‘trained immunity’, induces potent heterologous protection against infections. I propose that induction of trained immunity is an important novel approach to improved vaccination in the elderly. Induction of trained immunity is regulated by the interaction between the host genome, microbiome, and the epigenetic and metabolic programs of specific populations of myeloid cells, and we need to understand how these factors are impacted by age and gender of the host. By understanding the factors that impact the response to BCG (Bacille Calmette-Guerin), the prototype vaccine that induces trained immunity, we will be able to design better vaccines for the elderly. The Key objectives of the project are: Key objective 1: To describe the innate immune cell (sub)populations, and their heterogeneity at single-cell level, responsible for mediating trained immunity in the young and elderly adults. Key objective 2: To identify the complex genetic, epigenetic, microbiome, and metabolic programs that represent the molecular and biochemical substrates of trained immunity in the myeloid cells of the elderly individuals. Key objective 3: To use systems biology to map the heterogeneity of trained immunity response determined by host (epi)genome, microbiome, and environmental factors in the elderly. Expected results: We will understand the main cellular and molecular mechanisms for the induction of trained immunity responses in vivo and the specificities of the response in the elderly. These findings will enable the design of innovative approaches to improve vaccination strategies.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-ADG - Advanced Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2018-ADG

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Host institution

STICHTING RADBOUD UNIVERSITAIR MEDISCH CENTRUM
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 262 500,00
Address
GEERT GROOTEPLEIN 10 ZUID
6525 GA NIJMEGEN
Netherlands

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Region
Oost-Nederland Gelderland Arnhem/Nijmegen
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 262 500,00

Beneficiaries (3)

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