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Importance of antibodies to lipopolysaccharide in natural and vaccine-induced serum bactericidal activity against Neisseria meningitidis group B.
- Source :
-
Infection and immunity [Infect Immun] 2011 Oct; Vol. 79 (10), pp. 4146-56. Date of Electronic Publication: 2011 Jul 18. - Publication Year :
- 2011
-
Abstract
- Analysis of the specificity of bactericidal antibodies in normal, convalescent, and postvaccination human sera is important in understanding human immunity to meningococcal infections and can aid in the design of an effective group B vaccine. A collection of human sera, including group C and group B convalescent-phase sera, normal sera with naturally occurring cross-reactive bactericidal activity, and some postvaccination sera, was analyzed to determine the specificity of cross-reactive bactericidal antibodies. Analysis of human sera using a bactericidal antibody depletion assay demonstrated that a significant portion of the bactericidal activity could be removed by purified lipopolysaccharide (LPS). LPS homologous to that expressed on the bactericidal test strain was most effective, but partial depletion by heterologous LPS suggested the presence of antibodies with various degrees of cross-reactivity. Binding of anti-L3,7 LPS bactericidal antibodies was affected by modification of the core structure, suggesting that these functional antibodies recognized epitopes consisting of both core structures and lacto-N-neotetraose (LNnT). When the target strain was grown with 5'-cytidinemonophospho-N-acetylneuraminic acid (CMP-NANA) to increase LPS sialylation, convalescent-phase serum bactericidal titers were decreased by only 2- to 4-fold, and most remaining bactericidal activity was still depleted by LPS. Highly sialylated LPS was ineffective in depleting bactericidal antibodies. We conclude that natural infections caused by strains expressing L3,7 LPS induce persistent, protective bactericidal antibodies and appear to be directed against nonsialylated bacterial epitopes. Additionally, subsets of these bactericidal antibodies are cross-reactive, binding to several different LPS immunotypes, which is a useful characteristic for an effective group B meningococcal vaccine antigen.
- Subjects :
- Adolescent
Antibodies, Bacterial immunology
Child
Child, Preschool
Cross Reactions
Double-Blind Method
Humans
Infant
Meningococcal Infections immunology
Meningococcal Infections microbiology
Meningococcal Vaccines administration & dosage
Treatment Outcome
Young Adult
Antibodies, Bacterial blood
Blood Bactericidal Activity immunology
Lipopolysaccharides immunology
Meningococcal Infections prevention & control
Meningococcal Vaccines immunology
Neisseria meningitidis, Serogroup B immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5522
- Volume :
- 79
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Infection and immunity
- Publication Type :
- Academic Journal
- Accession number :
- 21768280
- Full Text :
- https://doi.org/10.1128/IAI.05125-11