Although we quantitatively show that BnAbs that bind to Group 1 and 2 HAs are present at very low levels, as well as that stem pocket-directed F10-like BnAbs exist at even lower levels, the question of whether serum or IVIG has protective levels of either type of heterosubtypic BnAbs is not answered in our study. However, our quantitative data support the notion that the levels of these BnAbs are borderline or below titers that would traditionally be considered protective. For example, there is up to 1 lg of F10-like Abs/100 mg IVIG; assuming 10 mg/mL IgG in normal human serum, then concentrations up to 0.1 lg/ ml of F10-like Ab could be present. Likewise, the fraction of acid eluted BnAbs with activities against Groups 1 and 2 could also be in this range. Furthermore, we did observe variability in these levels in our study patients (Figure 1) , and it remains possible that host factors, including VH polymorphism, may impact the baseline and inducible BnAb levels. In addition, the origins of these 2 populations of heterosubtypic anti-HA Abs are unknown. The possibility that they may be a component of ''natural'' polyreactive Abs cannot be excluded [22] . However, it is most likely that both our H5N1 vaccine study subjects and the IVIG donors had prior exposure to other Group 1 (H1N1) and Group 2 (H3N2) influenza A viruses, either through seasonal vaccinations and/or natural infection, and this may have given rise to heterosubtypic H5 and H7 binding Abs, respectively.