Flu B bnAb-Result 3-2

Despite the efficacy of oseltamivir being limited, especially when the treatment is delayed, severely ill influenza patients are generally given oseltamivir upon hospital admission. Therefore, we tested whether coadministration of C12G6 and oseltamivir provided better protective efficacy than either treatment alone. Mice infected with MA-B/Florida/ 4/2006 or MA-B/Brisbane/60/2008 were treated, starting at 48 hours after infection, with C12G6, oseltamivir, or a combination of these two therapies. Mice receiving oseltamivir plus control C5G6 antibody exhibited 100% mortality by day 9 after lethal challenge with both lineages of influenza B virus, similar to the control group (C5G6 plus water). Administration of C12G6 plus water only partially protected animals, with survival rates of 40 and 60% for the Yamagata and Victoria strains, respectively. In contrast, coadministration of C12G6 with oseltamivir completely protected mice after lethal challenge with the two influenza B virus lineages (Fig. 4, C and D). Coadministration also resulted in reduced weight loss in mice, compared to treatment with either active agent alone (Fig. 4, E and F). Finally, consistent with the survival and bodyweight data, combined treatment considerably reduced lung viral titers at days 4 and 6, compared with C12G6 or oseltamivir alone (Fig. 4, G and H). To further estimate the protective potential of C12G6 in vivo, we determined the prophylactic and therapeutic windows for treating ferrets infected with B/Florida/4/2006 (Yamagata lineage) or B/Brisbane/ 60/2008 (Victoria lineage). As expected, nasal wash viral titers for ferrets treated with C12G6 either prophylactically or therapeutically were considerably lower than for those treated with control antibody, for both virus infections (Fig. 5, A to D). In addition, C12G6 treatment resulted in fever reduction after infection with each of the two viruses, in comparison to control antibody–treated animals (Fig. 5, E to H). Moreover, infected animals administered C12G6 only experienced slight body weight loss; in contrast, considerable body weight loss was observed in control antibody–treated animals (fig. S15). Consistent with the data above, all control ferrets showed clinical signs of infection, including nasal discharge, sneezing, and inactivity, whereas a lesser proportion of ferrets treated with C12G6 displayed clinical signs (fig. S16).