title: Specific immune responses and enhancement of murine pulmonary clearance of Moraxella catarrhalis by intranasal immunization with a detoxified lipooligosaccharide conjugate vaccine.
abstract: Moraxella catarrhalis is an important human mucosal pathogen. This study investigated the effect of intranasal immunization with a detoxified-lipooligosaccharide-cross-reactive mutant of diphtheria toxin (dLOS-CRM) vaccine candidate on pulmonary clearance following an aerosol challenge of mice with M. catarrhalis. Intranasal immunization with dLOS-CRM plus cholera toxin induced a significantly dose-dependent increase of immunoglobulin A (IgA) and IgG in the nasal wash, lung lavage fluid, saliva, and fecal extract. In addition, serum IgG, IgM, and IgA against LOS of M. catarrhalis were detected. LOS-specific antibody-forming cells were found in the nasal passages, spleens, nasally associated lymphoid tissues, cervical lymph nodes, lungs, and Peyer's patches using an enzyme-linked immunospot assay. The dLOS-CRM vaccine induced a significant bacterial clearance (70 to 90%) of both homologous and heterologous strains in the lungs compared to that observed in the controls (P < 0.01). Intriguingly, intranasal immunization with dLOS-CRM showed a higher level of bacterial clearance compared with subcutaneous injections with dLOS-CRM. These data indicate that dLOS-CRM induces specific mucosal and systemic immunity through intranasal immunization and also provides effective bacterial clearance. On the basis of these results, we believe that dLOS-CRM should undergo continued testing to determine whether it would induce protective immune response in humans.
authors.affiliation: National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850, USA.
authors.forename: Xinan
authors.initials: X
authors.lastname: Jiao
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirano
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Hou
authors.forename: Xin-Xing
authors.initials: XX
authors.lastname: Gu
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000921:Antibody-Producing Cells / Q000502:physiology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004167:Diphtheria Toxin / Q000276:immunology; D007114:Immunization; D008070:Lipopolysaccharides / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D001936:Moraxella catarrhalis / Q000276:immunology*; D018074:Vaccines, Conjugate; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D004167:Diphtheria Toxin; D008070:Lipopolysaccharides; D018074:Vaccines, Conjugate; D015164:Vaccines, Inactivated; C023023:lipid-linked oligosaccharides