Broadly reactive antibodies binding both pandemic H1N1 strains and common annual H1N1 strains have been identified both in humans Xu et al., 2010) and in mice (Manicassamy et al., 2010) . It is notable that three of five of the HA globular-head-binding antibodies induced by pandemic H1N1 infection were also broadly reactive to various H1N1 strains (Fig. 3 B) . One such novel antibody was the SF1009-3B06 antibody that reacts strongly with the pandemic H1N1 strain, as well as all recent H1N1 vaccine strains (Fig. 3 B and Fig. S2 A) . The precise epitope to which the 1009-3B06 antibody binds appears to be quite unique; it is only accessible on whole virions, not on recombinant HA, suggesting that the epitope is quaternary in nature. Finally, two antibodies cross-reacted and inhibited hemagglutination Figure 5 . In vivo prophylactic and therapeutic efficacy of human mAbs against pandemic H1N1 influenza virus. 6-8-wkold BALB/c mice were infected with a 3xLD50 dose of highly pathogenic, mouse-adapted 2009 pandemic H1N1 influenza (A/California/ 04/09). 24, 48, and 60 h after infection, 200 µg (10 mg/kg of body weight) of EM-4C04, 70-F02, or 1009-3B06 human mAb were injected intraperitoneally. All mice were monitored daily for body weight changes and any signs of morbidity and mortality. Percentage of initial body weight is plotted, and the number of surviving mice is shown in the lower right of each plot. Infected, untreated mice showed clear signs of sickness around day 4-5 after infection and perished by day 8-9. Prophylactic treatment is shown on the left for comparison. Antibody treatment conferred significant protection as determined by comparison of weights in untreated versus prophylaxis and at the time of treatment versus 12 d after infection (unpaired, twotailed Student's t test, P < 0.05). The log-rank test indicated significant survival as well (P < 0.001). Figure shows one representative experiments of at least three independent repeat experiments.