Figure 5: In vivo efficacy of 46B8 compared with and in combination with Tamiflu.

(a) DBA/2 J mice were infected intranasally with a minimum lethal dose (left panels) or a high lethal dose (right panels) of B/Victoria/504/2000. At 72 h post infection, mice received a single treatment of 46B8 or a control IgG intravenously at 45 mg kg⁻¹, or Tamiflu orally at 100 mg kg⁻¹ twice a day for 5 days. Top panels: survival curves. Each group contains 12 mice. Log-rank tests of 46B8- versus Tamiflu-treated groups in both infection models give P<0.05. Bottom panels: percent of average BW of survived mice as compared with the average pre-infection weight. (b) DBA/2 J mice were infected intranasally with a high lethal dose of B/Victoria/504/2000. At 72 h post infection, mice received a single treatment of 46B8 or a control IgG intravenously at 45 mg kg⁻¹, Tamiflu orally at 100 mg kg⁻¹ twice a day for 3 days, or a combined treatment of 46B8 and Tamiflu. At day 3, 4 and 6 post infection, lung homogenates were prepared and viral titres in the homogenates were determined with a TCID₅₀ assay on MDCK cells. Titres are shown in TCID₅₀ ml⁻¹. Each group contains 10 mice. An unpaired two-tailed t-test of 46B8 versus Tamiflu and the combined treatment versus 46B8 or Tamiflu alone at day 4 and 6 give P<0.05. Dotted line: detection limit of the assay; arrow: treatment initiation point. (c) DBA/2 J mice were infected intranasally with a high lethal dose of B/Victoria/504/2000. At 72 h post infection, mice received a single treatment of 46B8 or a control IgG intravenously at 5 mg kg⁻¹, Tamiflu orally at 100 mg kg⁻¹ twice a day for 5 days, or a combined treatment of 46B8 and Tamiflu. Left panel: survival curves. Each group contains eight mice. A log-rank test of the combined treatment versus 46B8 alone gives P<0.05, and the combined treatment versus Tamiflu alone gives P=0.06. Right panel: percent of average BW of survived mice as compared with the average pre-infection weight. (a,c: mean and s.d.)