Outer-membrane antigen expression by Moraxella (Branhamella) catarrhalis influences pulmonary clearance

Moraxella (Branhamella) catarrhalis is a common respiratory tract pathogen in man. The bacterium shows a strong tendency to form aggregates in vitro. A variant strain of M. catarrhalis that showed a reduced tendency to form aggregates was selected by successive in-vitro passage in broth culture from which aggregates had settled. The nonclumping variant strain showed alteration in expression of outer-membrane antigens, including the HMW-OMP, an outer-membrane protein of c. 200 kDa, outer-membrane protein CD and lipo-oligosaccharide. A mouse model for pulmonary challenge with M. catarrhalis revealed significant differences in the rate of clearance of the isogenic variant strains from the lung. The parent strain caused enhanced recruitment of neutrophils to the lung and more rapid clearance of bacteria from the lungs in comparison to the nonclumping variant. It is concluded that alteration of expression of surface molecules byM. catarrhalis has a significant impact in an in-vivo model of pulmonary clearance

Investigation of mucosal immunisation in pulmonary clearance of Moraxella (Branhamella) catarrhalis

Moraxella (Branhamella) catarrhalis is a common cause of otitis media in children and respiratory infection in adults with chronic obstructive pulmonary disease. To identify immune responses that may facilitate the development of a mucosal vaccine, a mouse model to study pulmonary responses was established. Regimes involving intra-Peyer's patch, intratracheal and intranasal routes of immunisation with killed M. catarrhalis were investigated. A mucosal immunisation regime of a primary intra-Peyer's patch immunisation with an intratracheal boost resulted in significantly enhanced pulmonary clearance of bacteria compared to controls following an intratracheal challenge with live bacteria. Additional intratracheal boosts did not induce further enhancement of clearance. Intra-Peyer's patch immunisation alone, intratracheal and intranasal immunisations did notinduce enhanced clearance. The levels of specific IgG and IgA in serum and bronchoalveolar lavage ¯uid correlated with pulmonary clearance. The present study showed that mucosal immunisation induced enhanced pulmonary clearance of M. catarrhalis following live bacterial challenge. This mucosal immunisation model has demonstrated that a mucosal vaccine, particularly an oral vaccine, would be feasible

Role of an immunodominant T cell epitope of the P6 protein of nontypeable Haemophilus influenzae in murine protective immunity

Nontypeable Haemophilus influenzae (NTHI) is a common cause of otitis media in children and lower respiratory tract infection in adultswith chronic lung disease. The highly conserved P6 protein of NTHI infection is under evaluation as a vaccine antigen in several animalmodels. To elucidate the role of cellular immune response to P6 in protective immunity, the goal of this study was to identify and characterize T cell epitope(s) on P6 and to investigate the role of these epitope(s) in eliciting antigen specific antibody responses and in mediating pulmonary clearance of NTHI. We report that T cells from BALB/c immunized with P6 recognize a single, immunodominant region, represented by 15 amino acids (residues 41–55) of the P6 protein. To verify the ability of this epitope to elicit T cell responses to the P6 protein, mice were immunized with a synthetic peptide corresponding to the sequence of dominant peptide. T cells isolated from mice primed in vivo with the peptide responded following in vitro stimulation with either the peptide or with the whole P6 molecule. Substitution of single amino acids and N or C terminal truncations of the dominant peptide resulted in complete abrogation of the response, implicating their importance to the T cell response. Furthermore, mucosal immunization of mice with a chimeric peptide that encompassed the dominant T cell epitope and a putative B cell epitope resulted in enhanced bacterial clearance following pulmonary challenge with NTHI. Collectively, these results establish that, ina mouse model, P6 contains a single immunodominant T cell epitope and this epitope plays an important role in protective immune responsesinduced by immunization with P6

Enhancement of pulmonary clearance of Moraxella (Branhamella) catarrhalis following immunization with outer membrane protein CD in a mouse model

Moraxella (Branhamella) catarrhalis is an important human respiratory tract pathogen. Outer membrane protein (OMP) CD is highly conserved among strains and has characteristics that indicate it may be an effective vaccine antigen. This study investigated the effect of immunization with OMP CD on pulmonary clearance following intratracheal challenge of mice with M. catarrhalis. Two routes of immunization were studied: mucosal immunization (intra-Peyer’s patch followed by intratracheal boost) and intramuscular immunization withOMP CD. Both resulted in enhanced pulmonary clearance of M. catarrhalis compared with sham-immunized controls. Immunization with OMP CD induced specific antibodies in serum and bronchoalveolar lavage fluid and induced a specific lymphocyte proliferative response in T cells from mesenteric lymph nodes from mice mucosally immunized with OMP CD. On the basis of these results, OMP CD should undergo continued testing to determine whether it will induce a protective immune response in humans

Vaccines for otitis media : proposals for overcoming obstacles to progress

Otitis media is a common problem with enormous morbidity worldwide. The development of vaccines to prevent otitis media would have animportant human and economic impact. A striking lack of progress in the development, production and clinical testing of vaccines to prevent otitis media has occurred in the past decade. This review outlines a series of specific proposals intended to advance vaccine development for otitis media

Nontypeable Haemophilus influenzae as a pathogen in children

Nontypeable Haemophilus influenzae is a significant pathogen in children, causing otitis media, sinusitis, conjunctivitis, pneumonia, and occasionally invasive infections. H. influenzae type b conjugate vaccines have no effect on infections caused by nontypeable strains because nontypeable strains are nonencapsulated. Approximately, one-third of episodes of otitis media are caused by nontypeable H. influenzae and the bacterium is the most common cause of recurrent otitis media. Recent progress in elucidating molecular mechanisms of pathogenesis, understanding the role of biofilms in otitis media and an increasing understanding of immune responses have potential for development of novel strategies to improve prevention and treatment of otitis media caused by nontypeable H. influenzae. Feasibility of vaccination for prevention of otitis media due to nontypeable H. influenzae was recently demonstrated in a clinical trial with a vaccine that included the surface virulence factor, protein D

Panel 5: microbiology and immunology panel

The objective is to perform a comprehensive review of the literature from January 2007 through June 2011 on the virology, bacteriology, and immunology related to otitis media

Rocking the BOAT: the ups and downs of the long-term radio light curve for GRB 221009A

We present radio observations of the long-duration gamma-ray burst (GRB) 221009A that has become known to the community as the Brightest Of All Time or the BOAT. Our observations span the first 475 d post-burst and three orders of magnitude in observing frequency, from 0.15 to 230 GHz. By combining our new observations with those available in the literature, we have the most detailed radio data set in terms of cadence and spectral coverage of any GRB to date, which we use to explore the spectral and temporal evolution of the afterglow. By testing a series of phenomenological models, we find that three separate synchrotron components best explain the afterglow. The high temporal and spectral resolution allows us to conclude that standard analytical afterglow models are unable to explain the observed evolution of GRB 221009A. We explore where the discrepancies between the observations and the models are most significant and place our findings in the context of the most well-studied GRB radio afterglows to date. Our observations are best explained by three synchrotron-emitting regions that we interpret as a forward shock, a reverse shock, and an additional shock potentially from a cocoon or wider outflow. Finally, we find that our observations do not show any evidence of any late-time spectral or temporal changes that could result from a jet break but note that any lateral structure could significantly affect a jet break signature.</p