2.1.3  Rats
“True” rat species have been evaluated to determine their suitability as models for influenza disease and to ascertain whether genetic background impacts their susceptibility to infection. In one study, Brown Norway (BN), Fischer-344 (F344) and Sprague–Dawley (SD) rats were challenged with a rat-adapted influenzaA/Port/Chalmers/173 (H3N2) virus (Daniels et al., 2003). The virus was adapted to rats by 11 successive passages thorough infected lung homogenate. The F344 and SD rats were most sensitive to the infection, with 100-fold higher lung virus titers than seen in the BN rats. Alveolar macrophages, lactate dehydrogenase activity, and total lung protein concentrations (an indicator of pulmonary edema) were higher in the BN rats. Neutrophil numbers, interleukin 6 levels, and TNF-α activity were greatest in the bronchoalveolar lavage fluids from F344 and SD rats. Nevertheless, the infection was not lethal and few pathologic abnormalities were noted in the lungs. Although the study provided insights into factors of importance in protecting the host from influenza virus infections, rat models probably have not been characterized well enough to be recommended for use in evaluating anti-influenza therapies.
Recently Alarcon et al. (2007) demonstrated the use of the Brown Norway rat in evaluating influenza vaccines. Using microneedle technology for i.d. administration of three different types of influenza vaccines (Fluzone® 2003–2004 formulations and DNA plasmid-based vaccine) the investigators demonstrated in a rat model, that a whole inactivated virus elicited antibody responses to the corresponding wild type parent H3N2 and B strains. Animals treated with multiple doses of DNA plasmid vaccine also responded with antibody response to the parent strains.