title: Affinity-purified human immunoglobulin G that binds a lacto-N-neotetraose-dependent lipooligosaccharide structure is bactericidal for serogroup B Neisseria meningitidis.
abstract: 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.
authors.affiliation: Department of Pediatrics, Laboratory Medicine, University of California at San Francisco, San Francisco, California 94121, USA. stabrookm@peds.ucsf.edu
authors.forename: Michele M
authors.initials: MM
authors.lastname: Estabrook
authors.forename: Gary A
authors.initials: GA
authors.lastname: Jarvis
authors.forename: J
authors.initials: J
authors.lastname: McLeod Griffiss
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D002846:Chromatography, Affinity / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D016756:Immunoglobulins, Intravenous; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism*; D050296:Microbial Viability; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D009844:Oligosaccharides / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D008070:Lipopolysaccharides; D009844:Oligosaccharides; C023023:lipid-linked oligosaccharides; C013084:lacto-N-neotetraose