Observations that support the possible presence of heterosubtypic Abs of the broader type that bind Group 1 and 2 viruses have also been seen in children after primary influenza infection [13] and mucosal vaccination of experimental animals [14, 15] . In one study, a cross-neutralizing murine mAb with The binding levels are shown as optical density at 450 nm (OD 450). E, microneutralization assay (MN) titer against H5N1 virus; y-axis shows the Log 2 MN titer. F, Competition ELISA. Pre-and post-immune serum samples from H5N1 vaccinees were tested for their competition activity against a Group 1specific BnAb, F10, binding to H5-VN04. Serially diluted serum samples were mixed with 3 ng/mL Bio-F10 and applied to H5-coated ELISA plates. The serum competition for binding of Bio-F10 to H5 was determined by measuring the remaining binding of Bio-F10 using HRP-Streptavidin. The serum competition activity is shown as percentage of inhibition. For all panels except panel E, data at 1 representative serum dilution are shown, as follows: panel A, 1:270; panel B, 1:5120; panels C and D, 1:2430; and panel F, 1:90. For all panels, data are shown in a box and whiskers graph. The box extends from 25th percentile to the 75th percentile, with a line at the median. The whiskers above and below the box indicate the 95th and 5th percentiles, respectively. The dots above and below the whiskers are data points beyond the 95th and 5th percentiles. hemagglutination inhibition activity against Group 1 (H1, H2, H5, H9, and H13) and Group 2 (H3) was recovered from an intranasally vaccinated mouse. In contrast to the F10-like Abs, this mAb was directed to the globular head, and escape mutants were readily obtained [16] . Other animal vaccine studies have shown that antibodies to the fusion peptide and an HA2 linear peptide can have broad reactivity to Group 1 and 2 HAs [17] [18] [19] and neutralizing activity [20, 21] , respectively. Whether different quantitative amounts of Group 1-specific BnAbs and/or Group 1 and 2-directed BnAbs are elicited by vaccination or natural infection remains an important but unanswered question of our study.