Humoral and cellular immune responses to mRNA COVID-19 vaccinations in the elderly: A longitudinal study in Japan

This study examined the durability of humoral and cell-mediated immune responses to COVID-19 mRNA vaccines over six months, focusing on age-related changes.

SARS-CoV-2 uninfected Japanese subjects aged 20-99 who received two doses of mRNA COVID-19 vaccine were recruited. SARS-CoV-2 Spike IgG antibody (IgG) level in the serum and the levels of interferon (IFN)-γ in blood stimulated with SARS-CoV-2 specific antigens by QuantiFERON (QFN) SARS-CoV-2 assay were measured.

The IgG levels of 138 subjects declined significantly with age and time post-vaccination (p < 0.001). For participants aged 70 and above (n = 80), the IFN-γ levels, an indicator of cell-mediated immunity, also significantly declined over time (p < 0.05). However, in those under 70 (n = 58), the IFN-γ levels were maintained at three- and six months post-vaccination. There was no significant difference in IFN-γ levels between three- and six months post-vaccination for all 138 subjects, including CD4⁺ and CD8⁺ T cell counts. No correlation was observed between IgG antibody levels and secreted IFN-γ values. Multivariate regression analysis revealed a significant correlation between IgG levels and age. In contrast, IFN-γ levels were associated with CD4⁺ T cell counts, CD8⁺ T cell counts, and Performance Status Scores but not with age.

The findings suggest that while humoral immunity (IgG levels) decreases with age and time, cell-mediated immunity (IFN-γ levels) is relatively preserved in individuals under 70 up to six months post-vaccination. However, this immune response is significantly attenuated in older adults aged 70 and above, indicating age-related immunosenescence in long-term immunity following COVID-19 vaccination.