Although the resolution of the crystal structure will be necessary for the fine definition of the PN-SIA28 epitope, several important considerations may already be made. Firstly, it was previously speculated that the presence of an additional glycosilation site (Asn54 corresponding to His45 present on group 1 viruses) on the HA1 portion of the stem region in H3N2 viruses is the reason for the lack of anti-H3N2 activity of other mAbs with heterosubtypic activity limited to group 1 subtypes [25, 26, 30] . The present study demonstrates that this extra glycosilation site on H3N2 does not preclude PN-SIA28 binding and neutralizing activity against viruses belonging to this subtype ( Figure 2 ). The testing of HA alanine mutants for position His45 on H1N1 and Asn54 on H3N2, and the increased binding of PN-SIA28 to Asn54His mutant on H3N2, confirm that this key residue is particularly important for the interaction of PN-SIA28 with HA. However, other residues, including Lys57 and others not yet identified, certainly play an important role in the PN-SIA28 binding to HA, as shown by the lack of activity observed against the recent H3N2 isolates tested, as well as against the H7N2 isolate, despite a substantial identity in the studied region ( Figure 2 ).