Use of the Chinchilla Model to Evaluate the Vaccinogenic Potential of the Moraxella catarrhalis Filamentous Hemagglutinin-like Proteins MhaB1 and MhaB2

Abstract

Moraxella catarrhalis causes significant health problems, including 15–20% of otitis media cases in children and ∼10% of respiratory infections in adults with chronic obstructive pulmonary disease. The lack of an efficacious vaccine, the rapid emergence of antibiotic resistance in clinical isolates, and high carriage rates reported in children are cause for concern. In addition, the effectiveness of conjugate vaccines at reducing the incidence of otitis media caused by Streptococcus pneumoniae and nontypeable Haemophilus influenzae suggest that M. catarrhalis infections may become even more prevalent. Hence, M. catarrhalis is an important and emerging cause of infectious disease for which the development of a vaccine is highly desirable. Studying the pathogenesis of M. catarrhalis and the testing of vaccine candidates have both been hindered by the lack of an animal model that mimics human colonization and infection. To address this, we intranasally infected chinchilla with M. catarrhalis to investigate colonization and examine the efficacy of a protein-based vaccine. The data reveal that infected chinchillas produce antibodies against antigens known to be major targets of the immune response in humans, thus establishing immune parallels between chinchillas and humans during M. catarrhalis infection. Our data also demonstrate that a mutant lacking expression of the adherence proteins MhaB1 and MhaB2 is impaired in its ability to colonize the chinchilla nasopharynx, and that immunization with a polypeptide shared by MhaB1 and MhaB2 elicits antibodies interfering with colonization. These findings underscore the importance of adherence proteins in colonization and emphasize the relevance of the chinchilla model to study M. catarrhalis–host interactions.

Antibodies against In Vivo -Expressed Antigens Are Sufficient To Protect against Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei

“…E. coli TUNER carrying the plasmids pHisBatA and pGSTBatA was used to produce recombinant forms of the BatA protein joined to His and GST tags, respectively. Both proteins were extracted from inclusion bodies and purified under denaturing conditions as previously described (98,146). Purified Burkholderia oligosaccharide chains of LPS (OPS) and CPS were kindly provided by Donald E. Woods (University of Calgary).…”

The Autotransporter BpaB Contributes to the Virulence of Burkholderia mallei in an Aerosol Model of Infection

“…coli strain TUNER for the purpose of producing and purifying His- and GST-tagged BpaB proteins, respectively. Both proteins were extracted from inclusion bodies and purified under denaturing conditions as previously outlined by our laboratory [ 14 , 51 ]. Purified capsular polysaccharides (CPS) from the Burkholderia pseudomallei LPS - mutant strain MB100 [ 52 ] were kindly provided by Donald E. Woods at the University of Calgary.…”

Potential impact of a Moraxella catarrhalis vaccine in COPD

“…Most notably, the chinchilla model for nasopharyngeal colonization has shown promise for assessing potential vaccine antigens against M. catarrhalis [82, 83]. This model has also been used successfully with NTHi and S. pneumoniae to simulate nasopharyngeal colonization and middle ear infection [48, 84–86].…”