Since, a too robust challenge may prove, false negatively, a poor efficacy of a human vaccine candidate in the ferret model, and vice versa. Furthermore, the duration of the challenge read out period varies, as well as the types of samples collected and frequency of sampling. Often the design of
a challenge protocol is based on predefined end points and read outs, or may rely on results from historical experiments. Because of these variations in the assessment of vaccine efficacy, the comparison of the outcomes of vaccine studies may be hampered, therefore a certain way of standardization could prove useful Panobinostat price by providing clarity. Recently, we reported that CT-scanning allows quantification and characterisation of influenza-induced pulmonary lesions in living animals . We showed that the pulmonary ground-glass opacities observed by CT scanning corresponded mainly to areas of alveolar oedema, which is a major histological lesion Navitoclax in early influenza-induced pneumonia and can be used to quantify the aerated lung volume (ALV). The present study was performed to evaluate the immunogenicity and protective efficacy of an adjuvanted inactivated influenza pH1N1 vaccine for intranasal use in the ferret model. A group of six ferrets was intranasally immunised with this vaccine candidate and compared to a second group of six ferrets
that received intranasally administered PBS as placebo. These administrations were performed on study days 0, 21 and 42. All animals were subsequently intratracheally challenged with 106 median tissue culture infectious dose (TCID50) H1N1 A/The Netherlands/602/2009 virus on study day 70. The animals were monitored for vaccine induced serological and immunological responses and for infection related clinical and virological responses (data will be presented elsewhere). As novel read out parameter CT-scanning was performed 6 days prior, and daily after, virus inoculation on all twelve ferrets
to monitor influenza isothipendyl induced lung damage by quantifying alterations in the ALVs. The animals were sacrificed at 4 days post-inoculation (dpi) to evaluate pathological and virological parameters. The ferrets (Mustela putorius furo) were females of 8 months of age, seronegative for antibodies against current circulating influenza viruses, and Aleutian disease virus. Housing and handling was performed under biosafety level (BSL)-3+ conditions in negatively pressurized and high efficiency particulate air (HEPA)-filtered biocontainment isolator units, approved by an independent institutional laboratory animal ethics and welfare committee. General injection anaesthesia (ketamine 8 mg/kg and medetomidine-HCl 7.5 μg/kg body weight) was applied during handling and scanning. The animals (n = 6) were immunised three times with a 3 week interval with an adjuvanted inactivated vaccine. 200 μl of vaccine was intranasally administered and divided equally over both nostrils.