Animal models of invasive pneumococcal disease

Pneumococcal disease results when colonizing pneumococci in the nasopharynx successfully invade sterile sites. The first half of this chapter focuses on individual disease models and provides general descriptions of the commonly used models. It also discusses considerations important to the application of these models to studies of vaccine antigens and some of the pros and cons of each model. The latter half of the chapter presents experimental considerations that relate to animal models in general: the need for multiple models, inclusion criteria for experiments, and statistics. Bacteremia is a potential outcome in virtually all models of pneumococcal infection and is easily evaluated. The classic mouse model for assessing protective immunity has been the use of otherwise fatal infections following intraperitoneally (i.p.) challenge to detect the effects of active immunization or passive antibodies. As neonates and infants are a major target for pneumococcal vaccination, the murine model of intranasal challenge with aspiration has been adapted to 1-week-old mice, whose immune system corresponds to that of the human neonate, and 3-week-old mice, whose immune system corresponds to that of the human infant. Otitis media models in several animal species have been developed to evaluate vaccine effects. The classic model of otitis media was developed using the chinchilla and has been well reviewed by Giebink. Advantages and limitations of the various animal models of invasive pneumococcal diseases emphasize the importance of a careful selection of animal models to address different scientific questions.