Results obtained with the whole virus and those obtained with the H5 and N1 peptides are not in complete agreement (online Appendix Figure) . This fi nding can be explained on the basis of the substantial differences in the antigen presentation underlying the whole virus and peptides. Moreover, we observed that a high activation of specifi c cells at baseline (t0) was associated with a reduced specifi c response after vaccination (t1), which suggests that stimulation of pre-activated T cells with high dose of antigen could induce T-cell anergy (25) with consequent loss of immune response. Preliminary evidence also suggests that humoral crosstype immunity is targeting antigens differently from HA: sera from persons showing signifi cant neutralizing titers against infl uenza (H5N1) did not recognize insect cells expressing HA from the H5N1 subtype (not shown) and did not show HI activity against H5N1 subtype. N1 may possibly also be a target of humoral immunity, but additional experiments such as Western blot analysis or inhibition of NA activity (26) are needed to clarify this point.