Fig. 3: Fewer systemic adverse effects after the second dose are linked to the lower induction of spike-specific CD4⁺ T cells after the first dose.

a, Frequency of donors with AEs after vaccination. Post1 (n = 216) and Post2 (n = 214) (upper). Frequency of donors with AEs after the second vaccination in adults and older adults. Adults (n = 105) and older adults (n = 109) (lower). The number of donors who reported the specified AE is shown below each bar. Fisher’s exact test was used to compare the frequency of participants experiencing AEs by time points and age group. Antipyretics indicate the use of antipyretic medication. b, Concentration of anti-RBD IgG antibody and frequency of AIM⁺ CD4⁺ T cells after first and second doses according to the severity of local pain and fever after the second doses in both groups (n = 216). Multiple comparisons by grade of adverse event symptoms were performed using the Kruskal–Wallis test with Dunn’s post hoc test. Local pain: grade 0 (n = 25), grade 1 (n = 169), grade 2 (n = 16) and grade 3 (n = 4). Fever: grade 0 (n = 192), grade 1 (n = 17) and grade 2 (n = 5). c, Concentration of anti-RBD IgG antibody and frequency of AIM⁺ and cytokine⁺ CD4⁺ T cells according to the emergence of fever after the second dose in adults (blue) or older adults (red). A comparison by fever grade in the age group was made using the Mann–Whitney test. Fever grade 0 (fever⁻; n = 86) and grade ≥ 1 (fever⁺; n = 19) in adults, fever⁻ (n = 106) and fever⁺ (n = 3) in older adults. In b and c, the center line and error bars indicate the median and IQR. The dashed and dotted lines indicate cutoff and LOD, respectively.

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