Efficacy in Ferrets of Two Doses of H5N1 <i>ca</i> Viruses against Challenge with Homologous and Heterologous H5N1 <i>wt</i> Viruses

<div><p>Ferrets were immunized with two doses of 10⁷ TCID₅₀ of H5N1 1997 <i>ca</i> or H5N1 2004 <i>ca</i> viruses 1 mo apart and challenged 1 mo later with 10⁷ TCID₅₀ of either H5N1 1997 <i>wt,</i> H5N1 2004 <i>wt,</i> or A/Indonesia/05/2005 (H5N1) <i>wt</i>. In order to determine the contribution of the internal protein genes of the AA <i>ca</i> virus to protection, an additional group of ferrets was immunized with H1N1 A/New Caledonia/99 <i>ca</i> and challenged with H5N1 1997 <i>wt</i>. These ferrets were not challenged with H5N1 2004 <i>wt</i> or A/Indonesia/05/2005 (H5N1) <i>wt</i>.</p> <p>Lungs, nasal turbinates, and brains were harvested 3 d after challenge and were homogenized and titered on MDCK cells. Three ferrets per group were evaluated. The lower limit of detection is indicated by the dashed line. *<i>p</i> < 0.05 compared to mock-immunized ferrets.</p>