Linked Life Data

21402895

Source:http://linkedlifedata.com/resource/pubmed/id/21402895

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2011-4-5
pubmed:abstractText
Ab-initiated, complement-dependent killing contributes to host defenses against invasive meningococcal disease. Sera from nonimmunized individuals vary widely in their bactericidal activity against group B meningococci. We show that IgG isolated from select individuals can block killing of group B meningococci by human sera that are otherwise bactericidal. This IgG also reduced the bactericidal efficacy of Abs directed against the group B meningococcal protein vaccine candidates factor H-binding protein currently undergoing clinical trials and Neisserial surface protein A. Immunoblots revealed that the blocking IgG was directed against a meningococcal Ag called H.8. Killing of meningococci in reactions containing bactericidal mAbs and human blocking Abs was restored when binding of blocking Ab to meningococci was inhibited using either synthetic peptides corresponding to H.8 or a nonblocking mAb against H.8. Furthermore, genetic deletion of H.8 from target organisms abrogated blocking. The Fc region of the blocking IgG was required for blocking because F(ab')(2) fragments were ineffective. Blocking required IgG glycosylation because deglycosylation with peptide:N-glycanase eliminated blocking. C4b deposition mediated by an anti-factor H-binding protein mAb was reduced by intact blocking IgG, but not by peptide:N-glycanase-treated blocking IgG, suggesting that blocking resulted from inhibition of classical pathway of complement. In conclusion, we have identified H.8 as a meningococcal target for novel blocking Abs in human serum. Such blocking Abs may reduce the efficacy of select antigroup B meningococcal protein vaccines. We also propose that outer membrane vesicle-containing meningococcal vaccines may be more efficacious if purged of subversive immunogens such as H.8.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
186
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4881-94
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed-meshheading:21402895-Amino Acid Sequence, pubmed-meshheading:21402895-Antibodies, Bacterial, pubmed-meshheading:21402895-Antibodies, Monoclonal, pubmed-meshheading:21402895-Bacterial Outer Membrane Proteins, pubmed-meshheading:21402895-Blood Bactericidal Activity, pubmed-meshheading:21402895-Blotting, Western, pubmed-meshheading:21402895-Dose-Response Relationship, Drug, pubmed-meshheading:21402895-Flow Cytometry, pubmed-meshheading:21402895-Humans, pubmed-meshheading:21402895-Immunoglobulin Fab Fragments, pubmed-meshheading:21402895-Immunoglobulin G, pubmed-meshheading:21402895-Microbial Viability, pubmed-meshheading:21402895-Molecular Sequence Data, pubmed-meshheading:21402895-Mutation, pubmed-meshheading:21402895-Neisseria meningitidis, pubmed-meshheading:21402895-Oligopeptides, pubmed-meshheading:21402895-Protein Binding
pubmed:year
2011
pubmed:articleTitle
Novel blocking human IgG directed against the pentapeptide repeat motifs of Neisseria meningitidis Lip/H.8 and Laz lipoproteins.
pubmed:affiliation
Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural