Abstract 978 Poster Session IV, Tuesday, 5/4 (poster 159)

Recently, heptavalent conjugate pneumococcal vaccines have been shown to prevent bacteremia in immunized infants; whether these vaccines will have a significant impact on pneumococcal colonization and mucosal disease, including pneumonia, is currently not known. Existing animal models of pneumococcal disease are highly virulent and therefore result in bacteremia, sepsis and high mortality. These models, therefore, may not be appropriate for the evaluation of vaccines for the prevention of non-bacteremic or mucosal pneumococcal disease. We sought to develop a non-bacteremic model of focal pneumococcal pneumonia in young rats. Challenge doses of Streptococcus pneumoniae serotypes 6b or 19f were prepared in Todd-Hewitt broth supplemented with 0.5% yeast extract and diluted in 0.5% low-gelling-point agarose. Twenty-one day-old Sprague-Dawley rats were injected transthoracically into the right lung with different doses of S. pneumoniae. We then evaluated clinical appearance, cultures of blood 1 and 4 days post-challenge, the presence of pneumonia by histopathology and 14-day mortality. (Table)

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Animals with pneumonia all had focal areas of consolidated lung parenchyma. The infiltrate consisted of both polymorphonuclear and monocytic cells, present in both the alveolar and bronchiolar spaces. All non-bacteremic animals with pneumonia appeared clinically well, as did animals without pneumonia. Pneumonia was not found in the left lung of any animal.

We established a model of pneumococcal pneumonia using challenge with lower inocula (104 to 102 colony-forming units) of S. pneumoniae. Focal pneumonia was reliably produced without associated bacteremia or death. We will be using this model in the evaluation of the protective effects of candidate pneumococcal vaccines (such as pneumococcal surface proteins) with respect to the prevention of non-bacteremic pneumococcal disease.