Moraxella catarrhalis is an important and emerging cause of infectious disease, including 15-20% of otitis media cases in children and ~10% of respiratory infections in adults with chronic obstructive pulmonary disease. Children have been reported to have a high carriage rate, there is not an efficacious vaccine, and there has been a rapid emergence of antibiotic resistance in clinical isolates. Additionally M. catarrhalis infections may become even more prevalent due to the effectiveness of conjugate vaccines at reducing the incidence of otitis media caused by Streptococcus pneumoniae and nontypeable Haemophilus influenzae. Hence, M. catarrhalis causes significant health problems and the development of a vaccine is highly desirable. Identifying potential vaccine candidates, testing their role in pathogenesis, and testing their ability to provide protection in an animal model are the first steps to developing a vaccine. To address this, we selected MhaB1 and MhaB2, which are part of a potential contact dependent inhibition system (CDI), as our candidates. To our knowledge, this is the first time a CDI system has been used in a vaccine study. The data demonstrate that MhaB1 and MhaB2 are CDI proteins and their cognitive immunity genes provide protection. Also, MhaB1 and MhaB2 play an important role in the ability of M. catarrhalis to colonize the chinchilla nasopharynx. Moreover, when vaccinated with portions of these proteins, the chinchillas produce MhaB specific antibodies, which decrease the ability of wild-type M. catarrhalis to colonize the chinchilla nasopharynx. In summary, this study describes the establishment of the chinchilla model to perform vaccine efficacy studies for M. catarrhalis, demonstrates that M. catarrhalis has a CDI system, and shows that this CDI system plays an important role in pathogenesis. To our knowledge, our data are the first report of testing a CDI system using an animal model.