Neisseria meningitidis serogroup B: laboratory correlates of protection

Vermont, C

doi:10.1016/s0928-8244(02)00342-5

Cited by 15 publications

(19 citation statements)

References 36 publications

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“…In the present study we were able to take advantage of a heightened awareness of meningococcal infection following the earlier institutional outbreak to undertake a longitudinal study of meningococcal carriage in a cohort of new students at the same university. In particular, we were able to follow students over a 7-month period and to examine the effect of carriage on individual immune responses and the development of SBA against serogroup B meningococci, the generally accepted "gold standard" correlate of protective immunity (35).…”

Section: Discussionmentioning

confidence: 99%

Development of Immunity to Serogroup B Meningococci during Carriage of Neisseria meningitidis in a Cohort of University Students

et al. 2004

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Understanding the basis of protective immunity is a key requirement for the development of an effective vaccine against infection with Neisseria meningitidis of serogroup B. We have conducted a longitudinal study into the dynamics of meningococcal acquisition and carriage in first-year university students. The detection of carriage of serogroup B meningococci correlated with an increase in detection of serum bactericidal activity (SBA) against both colonizing and heterologous serogroup B strains. Once induced, SBA remained high throughout the study. Although students showed increases in antibodies reactive with capsular polysaccharide and lipopolysaccharide (LPS), these antibody responses were transitory, and their decline was not accompanied by a corresponding decline in SBA. In contrast, there was a significant correlation between the presence of antibodies to the PorA outer membrane protein and SBA against both homologous and heterologous strains. SBA induced by a PorA-negative mutant confirmed the contribution of PorA to heterologous activity. Increases in SBA against a range of serogroup B strains were also observed in students in whom no meningococcal carriage was detected. This heterologous protection could not be associated with the presence of antibodies reacting with capsule, LPS, PorA, PorB, Rmp, Opa, Opc, or pilin, demonstrating that other, as yet unidentified, antigens contribute to the development of immunity to serogroup B meningococci. Identification of such antigens with the ability to induce an effective cross-reactive bactericidal response to a range of strains would be a major step in the production of a universally effective vaccine against infections caused by serogroup B meningococci.

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Section: Discussionmentioning

confidence: 99%

Development of Immunity to Serogroup B Meningococci during Carriage of Neisseria meningitidis in a Cohort of University Students

et al. 2004

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“…In the absence of a good animal model for meningococcal disease, the serum bactericidal activity assay is considered a good predictor for the protection against N. meningitidis serogroup B. 30 Remarkably, the bactericidal titers induced by peptide-A conjugate were higher than the titers induced by the OMV ( p , 0.01).…”

Section: Immunization Trialsmentioning

confidence: 99%

Immunogenicity of Peptide-vaccine Candidates Predicted by Molecular Dynamics Simulations

Oomen

Hoogerhout

Bonvin

et al. 2003

Journal of Molecular Biology

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We present an in silico, structure-based approach for design and evaluation of conformationally restricted peptide-vaccines. In particular, we designed four cyclic peptides of ten or 11 residues mimicking the crystallographically observed b-turn conformation of a predicted immunodominant loop of PorA from Neisseria meningitidis. Conformational correctness and stability of the peptide designs, as evaluated by molecular dynamics simulations, correctly predicted the immunogenicity of the peptides. We observed a peptide-induced functional antibody response that, remarkably, exceeded the response induced by the native protein in outer membrane vesicles, without losing specificity for related strains. The presented approach offers tools for a priori design and selection of peptide-vaccine candidates with full biological activity. This approach could be widely applicable: to outer membrane proteins of Gram-negative bacteria, and to other epitopes in a large range of pathogens.

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“…In the current study, we therefore cloned and expressed MIP as a recombinant protein and tested its ability to induce functional bactericidal antibodies, the generally accepted laboratory correlate of protection for serogroup B meningococci (52), using a variety of adjuvant formulations suitable for human use. ) was isolated from an outbreak of meningococcal infection that occurred in Stroud, Gloucestershire, United Kingdom, in the mid-1980s (37).…”

mentioning

confidence: 99%

The Neisseria meningitidis Macrophage Infectivity Potentiator Protein Induces Cross-Strain Serum Bactericidal Activity and Is a Potential Serogroup B Vaccine Candidate

et al. 2011

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A gene encoding a 29-kDa protein from Neisseria meningitidis serogroup B strain MC58 with homology to the macrophage infectivity potentiator (MIP) protein of Legionella pneumophila was cloned and expressed in Escherichia coli, and the purified soluble recombinant protein (rMIP) was used for immunization studies. Analysis of the predicted amino acid sequences of MIP from 13 well-characterized meningococcal strains, isolated from carriers or patients and differing in serogroup, serotype, and subtype, showed that the protein was highly conserved (98 to 100%), with only three distinct sequence types (designated I, II, and III) found. Western blotting showed that the MIP protein was expressed at similar levels by all of these strains. Immunization of mice with type I MC58 rMIP in detergent micelles and liposomes containing monophosphoryl lipid A (MPLA) induced high levels of surface-reactive antibodies with serum bactericidal activity (SBA) titers of 1/1,024 against the homologous strain. Bactericidal antibodies were also induced with the protein in saline alone and liposomes alone (titers, 1/128) but not following adsorption to Al(OH) 3 . Significantly, antisera raised against type I rMIP administered in saline or liposomes killed strains of heterologous sequence types II and III with similar SBA titers (1/128 to 1/256). Taken together, these findings suggest that rMIP can provide cross-strain protection against meningococci and should be considered a potential antigen for inclusion in new vaccines against meningococcal infection.

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Neisseria meningitidis serogroup B: laboratory correlates of protection

Cited by 15 publications

References 36 publications

Development of Immunity to Serogroup B Meningococci during Carriage of Neisseria meningitidis in a Cohort of University Students

Development of Immunity to Serogroup B Meningococci during Carriage of Neisseria meningitidis in a Cohort of University Students

Immunogenicity of Peptide-vaccine Candidates Predicted by Molecular Dynamics Simulations

The Neisseria meningitidis Macrophage Infectivity Potentiator Protein Induces Cross-Strain Serum Bactericidal Activity and Is a Potential Serogroup B Vaccine Candidate

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