Figure 2.

The spike-specific immune response declines with age

(A–C) Bottom 10 and top 10 expanders were determined as described in Figure 1E and analyzed for (A) age, (B) frequencies of SARS-CoV-2 spike-reactive Tmem pre-vaccination, and (C) the proportion of CD45RA⁻ Tmem cells within spike-reactive cells pre-vaccination.

(D) Representative CD45RA and CCR7 staining of total CD4⁺ T cells (upper plots) and spike-reactive CD154⁺ cells pre-vaccination of a young (<25 years) and old (>80 years) individual. Percentages of naive and memory cells and absolute cell counts of enriched spike-reactive T cells are indicated.

(E) Frequencies of spike-reactive memory cells pre-vaccination in different age groups.

(F) Vaccination-induced expansion of spike-reactive memory cells in the two representative donors from (D).

(G) Vaccination-induced expansion of spike-reactive memory cells in different age groups. (≤25, n = 11; 26–39, n = 21; 40–60, n = 12; >80, n = 6).

(H) Frequencies of spike-reactive CD4⁺ Tmems post-first, post-second, or post-third vaccination in different age groups.

(I) Serum anti-spike IgG concentrations 6–8 weeks or 6 months post-second vaccination or post-third vaccination in different age groups.

(J) SARS-CoV-2 serum neutralization titers 6–8 weeks post-second vaccination. Each symbol in (A–C) and (E–J) represents one donor; box-and-whisker plots display quartiles and range in (A–C). Horizontal lines indicate geometric mean in (E, H, I, J). Statistical differences: two-tailed Mann-Whitney test in (A–C); Kruskal-Wallis test with Dunn’s post hoc test in (E, H, I, J). See also Figure S3.