Maad Rayan Publishing Company Biomedicine Advances 3080-0382 3 2 2026 04 27 Aging may alter immune responses to COVID-19 vaccination 72 82 10.34172/bma.61 EN Maryam Sadri https://orcid.org/0000-0002-2358-6513 Sama Sadri Hossein Khorramdelazad Mohammad Reza Bolouri Ahmad Vosughi Motlagh https://orcid.org/0000-0001-9247-9757 REVIEW 10.34172/bma.61 2025 12 28 2026 03 09 The immune system weakens with age through immunosenescence, making older adults more vulnerable to infections and cancers. Viral pandemics like COVID-19 hit this group hardest, with the elderly facing the highest infection and death rates, especially those with underlying conditions. With the global older population expected to double by 2050, future outbreaks will continue to target this age group. Recent vaccine research shows that aging alters immune responses in complex ways. While older individuals may produce similar levels of neutralizing antibodies after repeated vaccination, other protective functions, like antibody-dependent cellular cytotoxicity, decline significantly. The broad immunity that defends against multiple virus strains also appears impaired in the elderly. Given these findings and the limitations of herd immunity strategies, strengthening elderly immune systems through proper nutrition, healthy lifestyles, and tailored vaccination approaches is critical. Standard vaccines may not be enough. Designing vaccines and schedules specifically to overcome aging-related immune weaknesses should be a priority for protecting this growing population against future pandemics.