Problems in the definition of meningococcal serotypes

Poolman, Jan; Hopman, C. T. P.; Zanen, H. C.

doi:10.1111/j.1574-6968.1982.tb08284.x

Cited by 55 publications

(7 citation statements)

References 43 publications

(37 reference statements)

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“…The 3125 strain was selected to fulfill this criterion. Moreover, using adsorbed rabbit polyclonal antibodies and immunoprecipitation (assays conducted by C. T. P. Hopman, University of Amsterdam, Department of Medical Microbiology, Amsterdam, The Netherlands; data not shown) (8,20,24) and Tricine-SDS-PAGE (Fig. 1), the LOS immunotypes of the A1, F8238, and 3125 meningococcal strains were confirmed to belong to immunotypes L8, L11, and L10, respectively.…”

Section: Resultsmentioning

confidence: 99%

Measurement of Functional Anti-Meningococcal Serogroup A Activity Using Strain 3125 as the Target Strain for Serum Bactericidal Assay

Poolman

Vleeschauwer

Durant

et al. 2011

Clin. Vaccine Immunol.

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Functional anti-N. meningitidis serogroup A (MenA) activity in human serum is detected by serum bactericidal assay (SBA), using either rabbit (rSBA) or human (hSBA) complement, with F8238 as the recommended MenA SBA target strain. However, the F8238 strain may not be optimal for this purpose because, as we show here, it expresses the L11 immunotype, whereas most MenA invasive strains express the L(3,7)9 or L10 immunotype. Moreover, SBA results may be strain dependent, because immunotypes differ in their sensitivity to complement, emphasizing the need to choose the most appropriate strain. Sera from random subsets of infants, toddlers, children, and adolescents in clinical trials of MenA conjugate vaccines were tested by rSBA using strains 3125 (L10) and F8238 (L11). In unvaccinated subjects from all age groups, the percentages of seropositive samples (rSBA-MenA titer, >1:8) was lower using strain 3125 than using strain F8238. However, in toddlers and adolescents immunized with a conjugate MenA vaccine, the percentages of seropositive samples generally were similar using either strain in the rSBA. In two studies, sera also were tested with hSBA. Using hSBA, the differences in the percentages of seroprotective samples (hSBA-MenA titer, >1:4) between strains 3125 and F8238 was less apparent, and in contrast with rSBA, the percentage of seroprotective samples from unvaccinated subjects was slightly higher using strain 3125 than using strain F8238. In adults vaccinated with plain MenA polysaccharide, the percentage of seroprotective samples was higher using strain 3125 than with strain F8238, and the vaccine response rates using strain 3125 were better aligned with the demonstrated efficacy of MenA vaccination. In conclusion, SBA results obtained using the MenA L10 3125 strain better reflected vaccine-induced immunity.The development of effective polysaccharide-protein conjugate vaccines targeting Neisseria meningitidis relies upon the measurement of bactericidal antibodies (4, 32). To ensure the quality, safety, and efficacy of N. meningitidis serogroup A (MenA) conjugate vaccines, the WHO recommends the use of any MenA strain in the serum bactericidal assay (SBA), provided that the strain is not killed by the complement in the absence of MenA-specific antibodies (33). However, strain A1, originally used by Goldschneider et al. in their classic studies (8), was shown to be too sensitive to complement killing (20). The SBA against MenA that has been proposed by Maslanka et al. (20) uses rabbit complement and MenA strain F8238.Clinical trials with MenA polysaccharide-protein conjugate vaccines showed a high percentage of control subjects, not vaccinated with a MenA vaccine, who became SBA positive (with rabbit complement 2nd strain F8238) between 18 weeks of age and the second year of life (5). However, these subjects did not display a parallel increase in anti-capsular polysaccharide A IgG, suggesting that part of the positive SBA results, referred to as natural immunity, was related to either noncapsular surface an...

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Section: Resultsmentioning

confidence: 99%

Measurement of Functional Anti-Meningococcal Serogroup A Activity Using Strain 3125 as the Target Strain for Serum Bactericidal Assay

Poolman

Vleeschauwer

Durant

et al. 2011

Clin. Vaccine Immunol.

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“…'-l' At present, 1 1 different LOS ITS are recognised : L1-L1 1 , of which L3, L7 and L9 are closely related immunochemically.3~ *, 8, l 2 The chemical structure of the terminal structures of Ll-L6 and L8 has been elucidated.13-ls Recently, two new LOS ITS (L12 and L13) were described among meningococci of serogroup A, but it is not yet clear whether they represent unique LOS structures. L9-Lll are found predominantly among serogroup A meningococci, and L2-L4 among serogroups B and C. [3][4][5]8,19,20 Knowledge of the distribution of LOS ITS among serogroup B meningococci might become of special interest, because the LOS is a potential vaccine candidate. 21 The aim of this study was to evaluate the applicability of the method of whole-cell ELISA (WCE) for LOS immunotyping with MAbs.…”

Section: Introductionmentioning

confidence: 99%

Lipo-oligosaccharide immunotyping of Neisseria meningitidis by a whole-cell ELISA with monoclonal antibodies

Scholten

Kuipers²,

Valkenburg

et al. 1994

Journal of Medical Microbiology

117

110

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“…In this context, the development of a LOS-based vaccine might be a valuable alternative. LOS of the immunotype L3,7 is observed in at least 70% of invasive MenB cases (29,33). In addition, it was already documented that L3,7 LOS induces the production of bactericidal antibod- a Results of the pyrogenicity assay according to European Pharmacopoeia.…”

Section: Discussionmentioning

confidence: 99%

“…The L3,7 immunotype (combined expression of L3 and L7) dominates in case isolates, representing up to 70% of disease cases, whereas another immunotype, L1,8, is most prevalent among carrier isolates (18,29,33). Differences in prevalence may be related to the composition of the different LOS immunotypes, which afford different adhesion/invasion and complement resistance properties (24,32,40).…”

Section: ) (3)mentioning

confidence: 99%

“…The fact that some cross-protection between L3,7 and L2 immunotypes was observed suggests that, in addition to anti-LOS antibodies, antibodies directed against OMPs were also involved in the bactericidal response induced by TrL3 and TrL2 OMVs. Immunotypes L3 and L2 represent the great majority of invasive serogroup B, C, W-135, and Y strains isolated from disease cases, with 70 to 80% expressing immunotype L3 and 20 to 30% expressing L2 (29,33). A L2/L3 bivalent formulation would have the potential to protect against the majority of invasive B, C, W-135, and Y strains.…”

Section: Vol 77 2009 Anti-los Antibodies For Antineisserial Cross-pmentioning

confidence: 99%

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Genetically Modified L3,7 and L2 Lipooligosaccharides from Neisseria meningitidis Serogroup B Confer a Broad Cross-Bactericidal Response

et al. 2009

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Currently available Neisseria meningitidis serogroup B (MenB) vaccines are based on outer membrane vesicles (OMVs) that are obtained from wild-type strains. They are purified with the aim of decreasing the lipooligosaccharide (LOS) content and hence reduce the reactogenicity of the vaccine even though LOS is a potential protective antigen. In <2-year-old children, these MenB vaccines confer protection only against strains expressing homologous PorA, a major and variable outer membrane protein. Our objective was to develop a safe LOS-based vaccine against MenB. To this end, we used modified porA knockout strains expressing genetically detoxified (msbB gene-deleted) L2 and L3,7 LOSs, allowing the production of LOSenriched OMVs. The vaccine-induced antibodies were found to be bactericidal against nearly all invasive strains, irrespective of capsular serogroup. In addition, we have also demonstrated that LOS lacking the terminal galactose (with a lgtB mutation; truncated L3 LOS), but not LOS produced without the galE gene, induced a bactericidal antibody response in mice similar to that seen for LOS containing the full lacto-Nneotetraose (L3,7 LOS). In conclusion, a bivalent detoxified LOS OMV-based vaccine demonstrated the potential to afford a broad cross-protection against meningococcal disease.The gram-negative Neisseria meningitidis serogroup B (MenB) is a major cause of bacterial meningitis in younger populations. The disease is associated with high morbidity and mortality rates, despite the availability of optimized treatments. Therefore, disease prevention by vaccination is considered a better approach than treatment. Currently available MenB vaccines are based on outer membrane vesicles (OMVs) that are obtained from wild-type strains and purified with the aim of decreasing the endotoxin lipooligosaccharide (LOS) content, hence reducing the reactogenicity of the vaccine. However, in Ͻ2-year-old children, these MenB vaccines confer protection only against strains expressing the homologous PorA, a major and variable outer membrane protein (OMP) present on the vaccine OMVs (25,34,43). Other vaccine approaches able to afford a larger cross-protection, among which the development of a safe LOS-based vaccine might be a valuable option, seem necessary. Indeed, antibodies to LOS have been shown to be bactericidal, both in humans (4) and in monkeys (45), and natural bacterial clearance in humans appears to be linked with anti-LOS activity (5). These two observations point out LOS as a potential vaccine candidate.LOS is composed of a lipid A anchor to the bacterial outer membrane and a variable glycan moiety. Although LOS has endotoxin properties, it behaves like an exotoxin due to the capacity of N. meningitidis to secrete large amounts of its outer membrane in the form of blebs or OMVs. Moreover, the fulminant cases of meningococcemia relate to a great extent to the amount of circulating LOS (2).Original immunotyping allowed the determination of 11 distinct LOS types among meningococcal strains, designated L1 to L11...

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Problems in the definition of meningococcal serotypes

Cited by 55 publications

References 43 publications

Measurement of Functional Anti-Meningococcal Serogroup A Activity Using Strain 3125 as the Target Strain for Serum Bactericidal Assay

Measurement of Functional Anti-Meningococcal Serogroup A Activity Using Strain 3125 as the Target Strain for Serum Bactericidal Assay

Lipo-oligosaccharide immunotyping of Neisseria meningitidis by a whole-cell ELISA with monoclonal antibodies

Genetically Modified L3,7 and L2 Lipooligosaccharides from Neisseria meningitidis Serogroup B Confer a Broad Cross-Bactericidal Response

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