“…Factors such as the age of the animals, the challenge dose, the challenge protocol and the role of other respiratory pathogens must be taken into account. A number of laboratories have reported success of their experimental vaccines after multiple challenges (up to three times) of young animals (ranging from 3 weeks to 5 months-old) with large doses of M. bovis (in the range of 10 9 to 10 10 colonyforming units [cfu]) [36][37][38]. In these reports, the success of the challenges is associated with the onset of clinical signs such as dyspnea, nasal discharge, moderate fever, weight loss, the presence of characteristic macroscopic lesions, such as lung consolidation, adhesions, and caseonecrotic pneumonic lesions; microscopic lung lesions, such as suppurative bronchiolitis, lymphoid hyperplasia, intra-alveolar and intrabronchial exudates, and coagulative necrosis, and isolation of M. bovis from challenged animals.…”