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The population of older adults is growing dramatically, especially in low and middle-income countries. With age, the immune system defects (e.g., immunosenescence) alter the capacity to eliminate pathogenic infections and respond effectively to vaccines. Adjuvants improve the immune response induced by vaccination; consequently, designing and testing novel adjuvants and elucidating their mechanism of action becomes imperative to develop more effective vaccines, particularly for older adults. Therefore, we aim to investigate the mechanism of action of multiple adjuvants during immunosenescence using in vitro and in vivo animal models and in vitro human primary cell models.