Age-related changes in the immune system and challenges for the development of age-specific vaccines.

Background: A better understanding of how the immune system evolves with age and how vaccines work in older people has led to increasing focus on the development of vaccines aimed specifically at older age groups. We discuss strategies used to improve vaccine immunogenicity for older adults, focusing on licensed adjuvants.

Findings: With age-related immune decline (immunosenescence), older adults face increased vulnerability to infections and severe complications. Immunosenescence affects T-cell and B-cell populations and innate immunity, leading to reduced chemotaxis, cytotoxicity, and altered cytokine production. This contributes to inflammaging-low-grade, chronic inflammation linked to aging. However, immune responses vary due to genetics and life-long exposures, making chronological age an imperfect indicator of immune health. Vaccination remains key to prevention, yet immune dysfunction complicates vaccine efficacy. Strategies to enhance responses in older adults include mRNA vaccines, high-antigen content vaccines, intradermal administration, and adjuvants. mRNA COVID-19 vaccines generated strong immune responses in older adults, though lower than in younger groups. High-antigen content influenza vaccines have shown superior efficacy compared to standard vaccination. Adjuvants offer a well-established approach to boosting vaccine responses by enhancing innate immunity.

Conclusions: Of various strategies used to improve immunogenicity of vaccines for older adults, adjuvants have been the most consistently effective and practical. More recently, mRNA vaccines have also shown great promise.