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. Aims: 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. Methods: 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. Results: 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-γ) 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. Conclusions: 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.