5 and 1.3, respectively (Table 2). In contrast, lungs in groups 3–6 (i.n.

Endocine™ adjuvanted pH1N1/09 vaccines) were much less affected with mean percentages of affected lung tissue of 7–8%. The RLWs in these four Endocine™-vaccinated groups were in line with these observations (in a close range of 0.8 to 0.9). The pulmonary consolidation corresponded with an acute broncho-interstitial pneumonia at microscopic examination. It was characterized by the presence of inflammatory cells (mostly macrophages and neutrophils) within the lumina and walls of alveoli, and swelling or loss of lining CHIR-99021 concentration pneumocytes. In addition protein rich oedema fluid, fibrin strands and extravasated erythrocytes in alveolar

spaces and type II pneumocyte hyperplasia were generally observed in the more severe cases of alveolitis. The histological parameters that were scored are summarized in Table 1. The most severe alveolar lesions were found in the control groups 1 (i.n. saline) and 2 (parenteral TIV). All parameters of alveolar lesions scored lowest KU55933 in group 5, but in fact the differences between the groups 3–6 were not significant. The development of pulmonary lesions was investigated by means of CT in ferrets of group 1 (i.n. saline), group 2 (s.c. TIV) and group 4

(i.n. Endocine™ adjuvanted split antigen at 15 μg HA), largely as described previously [29]. Consecutive in vivo imaging with CT scanning showed that ferrets of group 4 were largely protected against the appearance of pulmonary ground-glass opacities. Post infection reduction in aerated lung volumes (ALV) were measured from 3D CT reconstructs using lower and upper thresholds in substance densities of −870 to −430 HU. Ferrets of control group 1 showed a temporal Florfenicol significant increase in ALV on 1 dpi, as compared to both immunized groups 2 and 4 (Mann Whitney, two-tailed, p = 0.05) ( Fig. 3). Subsequently, the ferrets of group 1 showed a decrease of ALV at 2 dpi, which remained low on 3 and 4 dpi (group mean ALV ranging from 17.3 to −14.3%). Ferrets of group 4 were protected against major alterations in ALV (group mean ALV ranging from 0.95 to −7.8%), whereas ferrets of group 2 showed an intermediate decrease of ALV (group mean ALV ranging from 2.7 to −10.0%). Nasal influenza vaccines composed of inactivated pH1N1/09 split or whole virus antigen mixed with Endocine™ adjuvant induced high antibody titers in influenza naïve ferrets and protection against homologous challenge.