As shown in the online Appendix Figure, subtype (online Appendix Figure, panel B); among them, 3 were also showing an increase of the frequency of IFNγ-producing CD4 T cells specifi c for vaccine preparation (donors 11, 17, 42). Two of them, donor 11 and donor 42, had a signifi cant increase of IFN-γ-producing CD4 T cells specifi c for H5/N1 peptides (online Appendix Figure, panel C), which suggests that cross-type immunity may directly involve the HA/NA proteins. Furthermore, 3 other donors (donors 12, 16, 36) had an increased frequency of H5/N1 peptides-specifi c CD4 T cells, even if they were unable to respond to whole virus. Indeed, in some persons we also observed a signifi cant decrease at t1 in CD4 T cells specifi c for vaccine preparation (donors 2, 16, 23, 27, 30, 31, 35, 41) , specifi c for infl uenza (H5N1) (donors 4, 16, 27) , and specifi c for H5/N1 peptides (donors 2, 27, 34, 39, 41). Donors with a reduced specifi c response to vaccine preparation at t1 showed a higher frequency of specifi c CD4 T cells at t0 when compared to other donors (3.4% ± 0.88 vs. 1.29% ± 0.35, respectively, p = 0.013). Similar results were obtained when we observed the infl uenza virus (H5N1) (1.07% ± 0.47 vs. 0.14% ± 0.03, respectively, p = 0.0093) and H5/N1 peptides (1.19% ± 0.54 vs. 0.13% ± 0.07, respectively; p = 0.0018).