TRAIN-OLD SIGNED

Project "TRAIN-OLD" data sheet

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 Project 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.