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Infection and Immunity, February 2007, p. 1025-1033, Vol. 75, No. 2
0019-9567/07/$08.00+0     doi:10.1128/IAI.00882-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Affinity-Purified Human Immunoglobulin G That Binds a Lacto-N-Neotetraose-Dependent Lipooligosaccharide Structure Is Bactericidal for Serogroup B Neisseria meningitidis ^,

Michele M. Estabrook,^1* Gary A. Jarvis,^2,3 and J. McLeod Griffiss^2,3

Departments of Pediatrics,¹ Laboratory Medicine, University of California at San Francisco, San Francisco, California,² Veterans Affairs Medical Center, San Francisco, California³

Received 2 June 2006/ Returned for modification 2 August 2006/ Accepted 3 November 2006

Despite technological advances, no vaccine to prevent serogroup B meningococcal disease is available. The failure to develop a vaccine has shifted the focus to an alternative outer membrane structure, lipooligosaccharide (LOS), because disseminated disease induces bactericidal immunoglobulin G (IgG) that binds LOS. The purpose of this study was to identify the LOS structure(s) that induces human bactericidal IgG by purification and characterization of these antibodies. Human LOS IgG antibodies were affinity purified by passage of intravenous immunoglobulin through purified, type-specific LOS having a known structure coupled to epoxy-activated Sepharose 6B. Pathogenic group B strains representing the major LOS serotypes were used to examine the binding and bactericidal activities of four LOS-specific IgG preparations. All four LOS-specific IgG preparations bound to strains expressing homologous, as well as heterologous, LOS serotypes as determined by flow cytometry and an enzyme-linked immunosorbent assay. With human complement, IgG that was purified with L7 LOS was bactericidal for strains expressing L3,7 and L2,4 LOS, serotypes expressed by the majority of disease-associated group B and C meningococci. In conclusion, we purified human LOS-specific IgG that binds meningococci across LOS glycose-specific serotypes. An antigen that is dependent on the glycose lacto-N-neotetraose induces IgG in humans that is bactericidal for L2, L3, L4, and L7 strains. A vaccine containing this antigen would have the potential to protect against the vast majority of group B meningococcal strains.

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* Corresponding author. Mailing address: VAMC (111W1), 4150 Clement St., San Francisco, CA 94121. Phone: (415) 221-4810, ext. 3788. Fax: (415) 221-7542. E-mail: estabrookm{at}peds.ucsf.edu.

Published ahead of print on 13 November 2006.

Editor: J. N. Weiser

Paper 102 from the Center for Immunochemistry.

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Infection and Immunity, February 2007, p. 1025-1033, Vol. 75, No. 2
0019-9567/07/$08.00+0     doi:10.1128/IAI.00882-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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