| Candidacy of LPS-based glycoconjugates to prevent invasive meningococcal disease: developmental chemistry and investigation of immunological responses following immunization of mice and rabbits. | |
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MedLine Citation:
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PMID: 16046037 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glycoconjugates were prepared by covalently linking the immunogenic protein carrier CRM(197) to O-deacylated lipopolysaccharide (LPS) derived from Neisseria meningitidis (strain H44/76), immunotype L3 galE LPS. This mutant strain elaborates a truncated LPS structure that displays immunological epitopes characteristic of 76% of Group B meningococcal (NmB) strains. CRM(197) was covalently linked either to the reducing glucosamine residue of the lipid A region of the O-deacylated LPS or to a 2-keto-3-deoxy-octulosonic acid (Kdo) residue in the inner core region of the O-deacylated LPS. In both rabbits and mice a much stronger IgG response to the immunising antigen was generated in those animals that received conjugates linked via the lipid A region. Sera from mice that were immunized with these conjugates were assayed for their reactivity with LPS, both mutant and wild-type, of several homologous and heterologous NmB strains. Sera obtained from mice immunized with conjugates in which the carrier protein was linked via the Kdo moiety were only able to react with O-deacylated, but not fully acylated (native), LPS from the homologous strain. However, sera obtained from mice that were immunized with conjugates, in which the carrier protein was coupled to the lipid A region, reacted predominately with inner core epitopes that contained phosphoethanolamine at the same 3-position of the distal heptose residue (HepII) of the inner core LPS as was present on the immunising antigen. Additionally it was observed that sera from rabbits immunised with lipid A linked conjugates, unlike the mice responses, were generally not as specific for LPS antigens that contained phosphoethanolamine at the same 3-position as was present on the immunising antigen, but showed a broader inner core recognition, whereas those rabbits that received the Kdo-linked conjugates gave only a very weak non-specific response to all immunotypes. Finally, the sera from two out of six mice that had received lipid A linked conjugates had bactericidal activity against L3 wild-type NmB strain 8047 and one of these was able to passively protect against meningococcal infection in an infant rat model. This study demonstrates evidence towards the proof-in-principle that by using Nm inner core LPS conjugates coupled via the lipid A region with an intact phosphoethanolamine at the O-3 position of the HepII of the inner core LPS, it is possible to elicit functional and protective antibodies against meningococcal infection. |
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Authors:
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A D Cox; W Zou; M A J Gidney; S Lacelle; J S Plested; K Makepeace; J C Wright; P A Coull; E R Moxon; J C Richards |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Vaccine Volume: 23 ISSN: 0264-410X ISO Abbreviation: Vaccine Publication Date: 2005 Oct |
Date Detail:
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Created Date: 2005-09-21 Completed Date: 2005-12-07 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8406899 Medline TA: Vaccine Country: Netherlands |
Other Details:
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Languages: eng Pagination: 5045-54 Citation Subset: IM |
Affiliation:
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Institute for Biological Sciences, National Research Council, 100, Sussex Drive, Ottawa, Ont., Canada K1A 0R6. andrew.cox@nrc-cnrc.gc.ca |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Bacterial / analysis Lipopolysaccharides / administration & dosage, chemistry, immunology* Meningococcal Infections / immunology* Meningococcal Vaccines / immunology* Mice Mice, Inbred BALB C Neisseria meningitidis / immunology* Rabbits |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Bacterial; 0/Lipopolysaccharides; 0/Meningococcal Vaccines |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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