Overall, these results indicate that the region bound by PN-SIA28 encompasses residues on the HA stem, and that it is partially overlapping from the binding region of other human neutralizing antibodies with heterosubtipic neutralizing activity limited to influenza A group 1 viruses [25, 26, 27, 28, 29] or group 2 viruses [30, 31] . In addition, the region bound is also partially shared with FI6v3, an optimized human mAb able to crossneutralize influenza A group 1 and group 2 viruses [32] . Importantly, both the heavy chains of PN-SIA28 and FI6v3 derive from rearrangement of the same VH gene germline (VH3-30). As already hypothesized for the VH1-69 subfamily, widely shared among human mAbs with heterosubtypic neutralizing activity limited to group 1 viruses, the VH3-30 gene structure may be important in conferring the broader heterosubtypic activity observed for PN-SIA28 and FI6v3. The future definition of HA/ PN-SIA28 crystal structure and its comparison with HA/FI6v3 complex may help confirm the possible role of conserved VH3-30 residues in conferring such unusual neutralization properties.