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Infection and Immunity, November 2002, p. 5982-5989, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.5982-5989.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Specific Immune Responses and Enhancement of Murine Pulmonary Clearance of Moraxella catarrhalis by Intranasal Immunization with a Detoxified Lipooligosaccharide Conjugate Vaccine

National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850

Received 29 April 2002/ Returned for modification 5 June 2002/ Accepted 5 August 2002

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.

Editor: J. D. Clements

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