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Infection and Immunity, March 2001, p. 1358-1363, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1358-1363.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Functional Characteristics of a Protective Monoclonal Antibody against Serotype A and C Lipooligosaccharides from Moraxella catarrhalis

Wei-Gang Hu,1 Jing Chen,1 John C. McMichael,2 and Xin-Xing Gu1,*

Laboratory of Immunology, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850,1 and Wyeth-Lederle Vaccines and Pediatrics, West Henrietta, New York 145862

Received 11 August 2000/Returned for modification 19 October 2000/Accepted 14 December 2000

A monoclonal antibody (MAb), designated MAb 8E7 (immunoglobulin G3), specific for Moraxella catarrhalis lipooligosaccharide (LOS) was evaluated for its functional activity in vitro and in a mouse model of colonization. Enzyme-linked immunosorbent assay (ELISA) demonstrated that the MAb 8E7 could be prepared to a high titer against LOS of the homologous strain 035E, and that it had bactericidal activity. MAb 8E7 reacted with M. catarrhalis serotype A and C LOSs but not serotype B LOS, as measured by ELISA and Western blotting. On the basis of published structures of LOSs, this suggests that the epitope recognized by MAb 8E7 is directed to a common sequence of either alpha -GlcNAc-(1right-arrow2)-beta -Glc-(1right-arrow at the branch substituting position 4 of the trisubstituted Glc residue or a terminal tetrasaccharide alpha -Gal-(1right-arrow4)-beta -Gal-(1right-arrow4)-alpha -Glc-(1right-arrow2)-beta -Glc-(1right-arrow at the branch substituting position 6 of the trisubstituted Glc residue. In a whole-cell ELISA, MAb 8E7 reacted with 70% of the 30 wild-type strains and clinical isolates tested. Immuno-electron microscopy demonstrated that MAb 8E7 reacted with a cell surface-exposed epitope of LOS on strain O35E. MAb 8E7 inhibited the adherence of strain O35E to Chang conjunctival epithelial cells by 90%. Passive immunization with MAb 8E7 could significantly enhance the clearance of strain O35E from mouse lungs in an aerosol challenge mouse model. This enhanced bacterial clearance was inhibited when MAb 8E7 was absorbed by M. catarrhalis serotype A LOS, indicating that the M. catarrhalis LOS-directed antibody may play a major role in the enhancement of M. catarrhalis clearance from lungs. These data suggest that MAb 8E7, which recognizes surface-exposed LOS of M. catarrhalis, is a protective antibody against M. catarrhalis.

* Corresponding author. Mailing address: 5 Research Ct., Rockville, MD 20850. Phone: (301) 402-2581. Fax: (301) 402-4200. E-mail: guxx{at}nidcd.nih.gov.

Infection and Immunity, March 2001, p. 1358-1363, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1358-1363.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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Copyright © 2001 by the American Society for Microbiology. All rights reserved.