Humoral and Cellular Immune Responses Against SARS-CoV-2 Following COVID-19 Vaccination in Older Adults: A Systematic Review

Background: Evidence on the humoral and cellular immune responses to SARS-CoV-2 following COVID-19 vaccination in older adults is warranted. Aim(s): To synthesize and analyze the current evidence on humoral and cellular immune responses to both standard and booster COVID-19 vaccination in individuals aged 60 years and older. Method(s): Clinical trials and observational studies were included. Reviews, case series, letters to the editor, and similar publications were excluded. A selective literature search was conducted in the following databases: PubMed, Scopus, EMBASE, and Web of Science. The risk of bias and methodological quality of the included studies were assessed using the Newcastle-Ottawa Scale (NOS) and the Risk of Bias 2.0 (RoB 2) tool. Statistical analysis was conducted using Stata version 18 and Review Manager version 5.4.1. Result(s): Thirteen studies were included: eleven observational studies and two randomized clinical trials, evaluating humoral and cellular immune responses in 782 older adults. Messenger RNA vaccines were the most administered, particularly Pfizer-BioNTech (76.9%) and Moderna mRNA-1273 (23%). In most cases, immune responses were assessed after the second dose and booster doses. Most studies (61.5%) reported increased IgG titers specific to the SARS-CoV-2 Spike protein, while 23.1% reported a decrease. Regarding cellular immunity, 46.2% of the studies reported low interferon-gamma (IFN-gamma) levels post-vaccination, whereas 38.5% showed increases. These findings highlight the need for tailored vaccination strategies to address emerging variants, particularly in vulnerable populations such as older adults. Conclusion(s): In older adults receiving COVID-19 vaccination, humoral immunity tends to increase, whereas cellular responses are frequently diminished, reflecting age-related immunosenescence that may limit the durability and breadth of protection following vaccination in older adults. Copyright © 2025 by the authors.