Cross-reactive polyclonal antibodies to the inner core of lipopolysaccharide from Neisseria meningitidis

S. R. Andersen, T. Guthrie, G. R. Guile, J. Kolberg, S. Hou, L. Hyland, Simon Yuk Chun Wong

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Sera from mice immunized with native or detergent-extracted outer membrane vesicles derived from lipopolysaccharide (LPS) mutant 44/76 (Mu-4) of Neisseria meningitidis were analyzed for antibodies to LPS. The carbohydrate portion of 44/76 (Mu-4) LPS consists of the complete inner core, Glcbetal-->4[GlcNAc alphal-->2Hep alpha1-->3]Hep alpha1-->5KDO[4-->2alphaKDO]. Immunoblot analysis revealed that some sera contained antibodies to wild-type LPS which has a fully extended carbohydrate chain of immunotype L3,7, as well as to the homologous LPS. Sera reacted only weakly to LPS from 44/76(Mu-3), which lacks the terminal glucose of the inner core. No binding to more truncated LPS was observed. Consequently, the cross-reactive epitopes are expressed mainly by the complete inner core. Dephosphorylation of wild-type LPS abolished antibody binding to LPS in all but one serum. Thus, at least two specificities of cross-reactive antibodies exist: one is dependent on phosphoethanolamine groups in LPS, and one is not. Detection of these cross-reactive antibodies strongly supports the notion that epitopes expressed by meningococcal LPS inner core are also accessible to antibodies when the carbohydrate chain is fully extended. Also, these inner core epitopes are sufficiently immunogenic to induce antibody levels detectable in polyclonal antibody responses. Meningococci can escape being killed by antibodies to LPS that bind only to a specific LPS variant, by altering the carbohydrate chain length. Cross-reactive antibodies may prevent such escape. Therefore, inner core LPS structures may be important antigens in future vaccines against meningococcal disease.

Original languageEnglish
Pages (from-to)1293-1300
Number of pages7
JournalInfection and Immunity
Volume70
DOIs
Publication statusPublished - 2002

Keywords

  • OUTER-MEMBRANE PROTEIN
  • MONOCLONAL-ANTIBODIES
  • LIPID-A
  • OLIGOSACCHARIDE EPITOPES
  • CAPSULAR POLYSACCHARIDE
  • VESICLE VACCINES
  • IMMUNOGENICITY
  • L1
  • L2
  • HETEROGENEITY

Cite this

Andersen, S. R., Guthrie, T., Guile, G. R., Kolberg, J., Hou, S., Hyland, L., & Wong, S. Y. C. (2002). Cross-reactive polyclonal antibodies to the inner core of lipopolysaccharide from Neisseria meningitidis. Infection and Immunity, 70, 1293-1300. https://doi.org/10.1128/IAI.70.3.1293-1300.2002

Cross-reactive polyclonal antibodies to the inner core of lipopolysaccharide from Neisseria meningitidis. / Andersen, S. R.; Guthrie, T.; Guile, G. R.; Kolberg, J.; Hou, S.; Hyland, L.; Wong, Simon Yuk Chun.

In: Infection and Immunity, Vol. 70, 2002, p. 1293-1300.

Research output: Contribution to journalArticle

Andersen, S. R. ; Guthrie, T. ; Guile, G. R. ; Kolberg, J. ; Hou, S. ; Hyland, L. ; Wong, Simon Yuk Chun. / Cross-reactive polyclonal antibodies to the inner core of lipopolysaccharide from Neisseria meningitidis. In: Infection and Immunity. 2002 ; Vol. 70. pp. 1293-1300.
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abstract = "Sera from mice immunized with native or detergent-extracted outer membrane vesicles derived from lipopolysaccharide (LPS) mutant 44/76 (Mu-4) of Neisseria meningitidis were analyzed for antibodies to LPS. The carbohydrate portion of 44/76 (Mu-4) LPS consists of the complete inner core, Glcbetal-->4[GlcNAc alphal-->2Hep alpha1-->3]Hep alpha1-->5KDO[4-->2alphaKDO]. Immunoblot analysis revealed that some sera contained antibodies to wild-type LPS which has a fully extended carbohydrate chain of immunotype L3,7, as well as to the homologous LPS. Sera reacted only weakly to LPS from 44/76(Mu-3), which lacks the terminal glucose of the inner core. No binding to more truncated LPS was observed. Consequently, the cross-reactive epitopes are expressed mainly by the complete inner core. Dephosphorylation of wild-type LPS abolished antibody binding to LPS in all but one serum. Thus, at least two specificities of cross-reactive antibodies exist: one is dependent on phosphoethanolamine groups in LPS, and one is not. Detection of these cross-reactive antibodies strongly supports the notion that epitopes expressed by meningococcal LPS inner core are also accessible to antibodies when the carbohydrate chain is fully extended. Also, these inner core epitopes are sufficiently immunogenic to induce antibody levels detectable in polyclonal antibody responses. Meningococci can escape being killed by antibodies to LPS that bind only to a specific LPS variant, by altering the carbohydrate chain length. Cross-reactive antibodies may prevent such escape. Therefore, inner core LPS structures may be important antigens in future vaccines against meningococcal disease.",
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T1 - Cross-reactive polyclonal antibodies to the inner core of lipopolysaccharide from Neisseria meningitidis

AU - Andersen, S. R.

AU - Guthrie, T.

AU - Guile, G. R.

AU - Kolberg, J.

AU - Hou, S.

AU - Hyland, L.

AU - Wong, Simon Yuk Chun

PY - 2002

Y1 - 2002

N2 - Sera from mice immunized with native or detergent-extracted outer membrane vesicles derived from lipopolysaccharide (LPS) mutant 44/76 (Mu-4) of Neisseria meningitidis were analyzed for antibodies to LPS. The carbohydrate portion of 44/76 (Mu-4) LPS consists of the complete inner core, Glcbetal-->4[GlcNAc alphal-->2Hep alpha1-->3]Hep alpha1-->5KDO[4-->2alphaKDO]. Immunoblot analysis revealed that some sera contained antibodies to wild-type LPS which has a fully extended carbohydrate chain of immunotype L3,7, as well as to the homologous LPS. Sera reacted only weakly to LPS from 44/76(Mu-3), which lacks the terminal glucose of the inner core. No binding to more truncated LPS was observed. Consequently, the cross-reactive epitopes are expressed mainly by the complete inner core. Dephosphorylation of wild-type LPS abolished antibody binding to LPS in all but one serum. Thus, at least two specificities of cross-reactive antibodies exist: one is dependent on phosphoethanolamine groups in LPS, and one is not. Detection of these cross-reactive antibodies strongly supports the notion that epitopes expressed by meningococcal LPS inner core are also accessible to antibodies when the carbohydrate chain is fully extended. Also, these inner core epitopes are sufficiently immunogenic to induce antibody levels detectable in polyclonal antibody responses. Meningococci can escape being killed by antibodies to LPS that bind only to a specific LPS variant, by altering the carbohydrate chain length. Cross-reactive antibodies may prevent such escape. Therefore, inner core LPS structures may be important antigens in future vaccines against meningococcal disease.

AB - Sera from mice immunized with native or detergent-extracted outer membrane vesicles derived from lipopolysaccharide (LPS) mutant 44/76 (Mu-4) of Neisseria meningitidis were analyzed for antibodies to LPS. The carbohydrate portion of 44/76 (Mu-4) LPS consists of the complete inner core, Glcbetal-->4[GlcNAc alphal-->2Hep alpha1-->3]Hep alpha1-->5KDO[4-->2alphaKDO]. Immunoblot analysis revealed that some sera contained antibodies to wild-type LPS which has a fully extended carbohydrate chain of immunotype L3,7, as well as to the homologous LPS. Sera reacted only weakly to LPS from 44/76(Mu-3), which lacks the terminal glucose of the inner core. No binding to more truncated LPS was observed. Consequently, the cross-reactive epitopes are expressed mainly by the complete inner core. Dephosphorylation of wild-type LPS abolished antibody binding to LPS in all but one serum. Thus, at least two specificities of cross-reactive antibodies exist: one is dependent on phosphoethanolamine groups in LPS, and one is not. Detection of these cross-reactive antibodies strongly supports the notion that epitopes expressed by meningococcal LPS inner core are also accessible to antibodies when the carbohydrate chain is fully extended. Also, these inner core epitopes are sufficiently immunogenic to induce antibody levels detectable in polyclonal antibody responses. Meningococci can escape being killed by antibodies to LPS that bind only to a specific LPS variant, by altering the carbohydrate chain length. Cross-reactive antibodies may prevent such escape. Therefore, inner core LPS structures may be important antigens in future vaccines against meningococcal disease.

KW - OUTER-MEMBRANE PROTEIN

KW - MONOCLONAL-ANTIBODIES

KW - LIPID-A

KW - OLIGOSACCHARIDE EPITOPES

KW - CAPSULAR POLYSACCHARIDE

KW - VESICLE VACCINES

KW - IMMUNOGENICITY

KW - L1

KW - L2

KW - HETEROGENEITY

U2 - 10.1128/IAI.70.3.1293-1300.2002

DO - 10.1128/IAI.70.3.1293-1300.2002

M3 - Article

VL - 70

SP - 1293

EP - 1300

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

ER -