Vaccination has been shown to be the most effective means of preventing infectious diseases, although older people commonly have a suboptimal immune response to vaccines and thus impaired protection against subsequent adverse outcomes. This Review provides an overview of the existing mechanistic insights into compromised vaccine response for respiratory infectious diseases in older people, defined as aged 65 years and older, including immunosenescence, epigenetic regulation, trained immunity, and gut microbiota. We further summarise the latest proven or potential strategies to strengthen weakened immunogenicity. Insights from these analyses will be conducive to the development of the next generation of vaccines.
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