Several human heterosubtypic neutralizing mAbs, directed against HA stem region and with protective features in animal models, have been recently described [20, 21, 22, 23, 24, 25] . All these mAbs recognize epitopes located in the most conserved region of influenza viruses HA and neutralize influenza viruses by blocking fusion of the viral and the host endosomal membranes. Many of these anti-influenza heterosubtypic neutralizing mAbs utilize the VH1-69 germline gene and bind to a hydrophobic region on the HA stem using their complementary determining region 2 (CDR2).