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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
-GlcNAc-(1
2)-
-Glc-(1
at the branch
substituting position 4 of the trisubstituted Glc residue or a terminal
tetrasaccharide
-Gal-(1
4)-
-Gal-(1
4)-
-Glc-(1
2)-
-Glc-(1
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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